diff --git a/src/Sentry.Profiling/SampleProfileBuilder.cs b/src/Sentry.Profiling/SampleProfileBuilder.cs
index 56927be4a9..3a90fe30a3 100644
--- a/src/Sentry.Profiling/SampleProfileBuilder.cs
+++ b/src/Sentry.Profiling/SampleProfileBuilder.cs
@@ -11,8 +11,12 @@ namespace Sentry.Profiling;
 internal class SampleProfileBuilder
 {
     private readonly SentryOptions _options;
+    private readonly SampleProfilerSession? _session;
     private readonly TraceLog _traceLog;
 
+    // The trim generation this builder's _stackIndexes cache was populated against.
+    private int _trimGeneration;
+
     // Output profile being built.
     public readonly SampleProfile Profile = new();
 
@@ -32,14 +36,30 @@ internal class SampleProfileBuilder
     // TODO make downsampling conditional once this is available: https://github.com/dotnet/runtime/issues/82939
     private readonly Downsampler _downsampler = new();
 
+    // For a TraceLog read from a file, where nothing trims it and no generation tracking is needed.
     public SampleProfileBuilder(SentryOptions options, TraceLog traceLog)
     {
         _options = options;
         _traceLog = traceLog;
     }
 
+    public SampleProfileBuilder(SentryOptions options, SampleProfilerSession session)
+        : this(options, session.TraceLog)
+    {
+        _session = session;
+        _trimGeneration = session.TrimGeneration;
+    }
+
     internal void AddSample(TraceEvent data, double timestampMs)
     {
+        // The interning tables have been discarded since we last looked so we have to
+        // invalidate the _stackIndexes cache (means stacks get walked again)
+        if (_session is { } session && _trimGeneration != session.TrimGeneration)
+        {
+            _trimGeneration = session.TrimGeneration;
+            _stackIndexes.Clear();
+        }
+
         var thread = data.Thread();
         if (thread is null || thread.ThreadIndex == ThreadIndex.Invalid)
         {
diff --git a/src/Sentry.Profiling/SampleProfilerSession.cs b/src/Sentry.Profiling/SampleProfilerSession.cs
index 376ba85a1c..06e6149f74 100644
--- a/src/Sentry.Profiling/SampleProfilerSession.cs
+++ b/src/Sentry.Profiling/SampleProfilerSession.cs
@@ -57,12 +57,29 @@ private SampleProfilerSession(SentryStopwatch stopwatch, EventPipeSession sessio
 
     public TraceLog TraceLog => EventSource.TraceLog;
 
+    // Bumped every time the interning tables are discarded. Anything caching a 
+    // CallStackIndex can invalidate it's cache whenever this changes
+    internal int TrimGeneration;
+
+    /// <summary>
+    /// Discards TraceLog's call stack interning tables, invalidating CallStackIndexes.
+    /// Must be called from the event processing thread.
+    /// </summary>
+    internal void TrimLiveSessionState()
+    {
+        OnTrimForTests?.Invoke();
+        TraceLog.TrimLiveSessionState();
+        TrimGeneration++;
+    }
+
     internal bool IsStopped => _stopped;
 
     internal static Action? BeforeStartupForTests;
 
     internal static Action<SampleProfilerSession>? OnSessionCreatedForTests;
 
+    internal static Action? OnTrimForTests;
+
     private static InterlockedBoolean _throwOnNextStartupForTests = false;
 
     internal static bool ThrowOnNextStartupForTests
diff --git a/src/Sentry.Profiling/SamplingTransactionProfiler.cs b/src/Sentry.Profiling/SamplingTransactionProfiler.cs
index 52d6ea193b..5436b29829 100644
--- a/src/Sentry.Profiling/SamplingTransactionProfiler.cs
+++ b/src/Sentry.Profiling/SamplingTransactionProfiler.cs
@@ -24,7 +24,7 @@ public SamplingTransactionProfiler(SentryOptions options, SampleProfilerSession
         _cancellationToken = cancellationToken;
         _startTimeMs = session.Elapsed.TotalMilliseconds;
         _endTimeMs = double.MaxValue;
-        _processor = new SampleProfileBuilder(options, session.TraceLog);
+        _processor = new SampleProfileBuilder(options, session);
         session.SampleEventParser.ThreadSample += OnThreadSample;
         cancellationToken.Register(() =>
         {
diff --git a/src/Sentry.Profiling/SamplingTransactionProfilerFactory.cs b/src/Sentry.Profiling/SamplingTransactionProfilerFactory.cs
index 6afc75538b..95ce64cfee 100644
--- a/src/Sentry.Profiling/SamplingTransactionProfilerFactory.cs
+++ b/src/Sentry.Profiling/SamplingTransactionProfilerFactory.cs
@@ -16,6 +16,9 @@ internal class SamplingTransactionProfilerFactory : IDisposable, ITransactionPro
 
     private const int SHUTDOWN_TIMEOUT_MS = 2_000;
 
+    // Once the interning tables exceed this many entries we discard them ASAP
+    internal int MaxCallStackCount = 100_000;
+
     private readonly SentryOptions _options;
 
     internal Task<SampleProfilerSession> _sessionTask;
@@ -31,6 +34,10 @@ internal bool IsDisposed
         get { lock (_sessionLock) { return _disposed; } }
     }
 
+    internal int TrimCount;
+
+    private bool _trimFailed;
+
     private bool _errorLogged = false;
 
     public SamplingTransactionProfilerFactory(SentryOptions options, TimeSpan startupTimeout)
@@ -54,6 +61,8 @@ public SamplingTransactionProfilerFactory(SentryOptions options, TimeSpan startu
             // This can block indefinitely.
             await session.WaitForFirstEventAsync(shutdownToken).ConfigureAwait(false);
 
+            session.SampleEventParser.ThreadSample += _ => TrimSessionStateIfNeeded(session);
+
             return session;
         });
 
@@ -137,6 +146,33 @@ private bool TryBeginShutdown(out SampleProfilerSession? sessionToStop)
         return null;
     }
 
+    /// <summary>
+    /// Must run on the event processing thread, which is the only thread allowed to trim - hence
+    /// hanging off ThreadSample rather than off profile completion.
+    /// </summary>
+    private void TrimSessionStateIfNeeded(SampleProfilerSession session)
+    {
+        if (_trimFailed || session.TraceLog.CallStacks.Count <= MaxCallStackCount)
+        {
+            return;
+        }
+
+        try
+        {
+            _options.LogDebug("Trimming profiler session state, {0} interned call stacks.", session.TraceLog.CallStacks.Count);
+            // Costs the in-flight sample: its stack mapping goes with the tables, so AddSample skips it.
+            session.TrimLiveSessionState();
+            TrimCount++;
+        }
+        catch (Exception e)
+        {
+            // Latch off rather than retrying on every subsequent sample, which would throw and log
+            // at sample rate on the event processing thread.
+            _trimFailed = true;
+            _options.LogError(e, "Failed to trim profiler session state. Profiling memory use is no longer bounded.");
+        }
+    }
+
     public void Dispose()
     {
         if (!TryBeginShutdown(out var session))
diff --git a/test/Sentry.Profiling.Tests/SamplingTransactionProfilerTests.cs b/test/Sentry.Profiling.Tests/SamplingTransactionProfilerTests.cs
index 03769e7057..1ba4e4f372 100644
--- a/test/Sentry.Profiling.Tests/SamplingTransactionProfilerTests.cs
+++ b/test/Sentry.Profiling.Tests/SamplingTransactionProfilerTests.cs
@@ -537,6 +537,155 @@ public void ProfilerIntegration_WithProfilingEnabled_SetsFactory()
         Assert.NotNull(hub.Options.TransactionProfilerFactory);
     }
 
+    [SkippableFact]
+    public void Profiler_WhenNoProfileRunning_TrimsInternedCallStacks()
+    {
+        Skip.If(TestEnvironment.IsGitHubActions, "Flaky in CI.");
+
+        // The interning tables grow whether or not a profile is running, so this deliberately never
+        // starts one - the trim has to happen off the back of ordinary samples. See #5469.
+        using var factory = new SamplingTransactionProfilerFactory(_testSentryOptions, TimeSpan.FromSeconds(30));
+        factory.MaxCallStackCount = 100;
+        SkipIfFailsInCI(() => factory._sessionTask.Wait(60_000));
+        var traceLog = factory._sessionTask.Result.TraceLog;
+
+        // Produce a variety of stack shapes so the sampler has something to intern. Run for the
+        // full duration rather than stopping at the first trim, so we observe the steady state.
+        var stopwatch = Stopwatch.StartNew();
+        var random = new Random(4242);
+        var highWaterMark = 0;
+        while (stopwatch.ElapsedMilliseconds < 3_000)
+        {
+            RecursiveWork(random.Next(8, 24), random);
+            highWaterMark = Math.Max(highWaterMark, traceLog.CallStacks.Count);
+        }
+
+        SkipIfFailsInCI(() =>
+        {
+            if (factory.TrimCount == 0)
+            {
+                throw new Exception($"No trim occurred; call stacks peaked at {highWaterMark}.");
+            }
+        });
+
+        Assert.True(factory.TrimCount > 0, $"Expected at least one trim, call stacks peaked at {highWaterMark}.");
+
+        // The table refills immediately after each trim, so its size at any instant is noise. What
+        // matters is that it stays bounded - untrimmed this workload reaches thousands in 3s.
+        Assert.True(highWaterMark < factory.MaxCallStackCount * 20,
+            $"Expected the interning table to stay bounded, but it peaked at {highWaterMark}.");
+    }
+
+    [SkippableFact]
+    public void Profiler_WhileProfileRunning_StillTrimsInternedCallStacks()
+    {
+        Skip.If(TestEnvironment.IsGitHubActions, "Flaky in CI.");
+
+        // A profile is held open for the whole test. Trimming must still happen: profiles can run
+        // back to back under load, so gating the trim on "no profile running" would starve it
+        // exactly when the tables grow fastest. The profile is then collected to show that trimming
+        // mid-profile does not corrupt its output.
+        using var factory = new SamplingTransactionProfilerFactory(_testSentryOptions, TimeSpan.FromSeconds(30));
+        factory.MaxCallStackCount = 100;
+        SkipIfFailsInCI(() => factory._sessionTask.Wait(60_000));
+
+        var clock = SentryStopwatch.StartNew();
+        var transactionTracer = new TransactionTracer(Substitute.For<IHub>(), "test", "");
+        var sut = factory.Start(transactionTracer, CancellationToken.None) as SamplingTransactionProfiler;
+        SkipIfFailsInCI(() => ArgumentNullException.ThrowIfNull(sut));
+        transactionTracer.TransactionProfiler = sut;
+
+        // Discard trims from before the profile started - the tiny budget means the session
+        // startup alone can trigger one. From here every trim happens while _inProgress is true.
+        factory.TrimCount = 0;
+
+        // Run for a fixed duration rather than stopping at the first trim: the profile needs to
+        // last long enough for samples to actually be dispatched to it, or there is nothing to
+        // validate at the end.
+        var stopwatch = Stopwatch.StartNew();
+        var random = new Random(4242);
+        while (stopwatch.ElapsedMilliseconds < 3_000)
+        {
+            RecursiveWork(random.Next(8, 24), random);
+        }
+
+        SkipIfFailsInCI(() =>
+        {
+            if (factory.TrimCount == 0)
+            {
+                throw new Exception("No trim occurred while a profile was running.");
+            }
+        });
+        Assert.True(factory.TrimCount > 0, "Expected trimming to happen even while a profile is running.");
+
+        sut!.Finish();
+        var elapsedNanoseconds = (ulong)((clock.CurrentDateTimeOffset - clock.StartDateTimeOffset).TotalMilliseconds * 1_000_000);
+        var collectTask = sut.CollectAsync(new SentryTransaction(transactionTracer));
+        collectTask.Wait();
+        ValidateProfile(collectTask.Result.Profile, elapsedNanoseconds);
+    }
+
+    [SkippableFact]
+    public void Profiler_WhenTrimFails_StopsRetrying()
+    {
+        Skip.If(TestEnvironment.IsGitHubActions, "Flaky in CI.");
+
+        var attempts = 0;
+        SampleProfilerSession.OnTrimForTests = () =>
+        {
+            attempts++;
+            throw new InvalidOperationException("Test exception");
+        };
+        try
+        {
+            using var factory = new SamplingTransactionProfilerFactory(_testSentryOptions, TimeSpan.FromSeconds(30));
+            factory.MaxCallStackCount = 100;
+            SkipIfFailsInCI(() => factory._sessionTask.Wait(60_000));
+
+            var stopwatch = Stopwatch.StartNew();
+            var random = new Random(4242);
+            while (stopwatch.ElapsedMilliseconds < 3_000)
+            {
+                RecursiveWork(random.Next(8, 24), random);
+            }
+
+            SkipIfFailsInCI(() =>
+            {
+                if (attempts == 0)
+                {
+                    throw new Exception("The trim was never attempted, so the latch was not exercised.");
+                }
+            });
+
+            // Without the latch this would be attempted on every sample for the rest of the session,
+            // throwing and logging each time on the event processing thread.
+            Assert.Equal(1, attempts);
+            Assert.Equal(0, factory.TrimCount);
+        }
+        finally
+        {
+            SampleProfilerSession.OnTrimForTests = null;
+        }
+    }
+
+    private static long RecursiveWork(int depth, Random random)
+    {
+        if (depth <= 0)
+        {
+            double sink = 0;
+            for (var i = 1; i < 5_000; i++)
+            {
+                sink += Math.Sqrt(i);
+            }
+            return (long)sink;
+        }
+
+        // Branch so that different calls produce different stack shapes.
+        return (random.Next(2) == 0)
+            ? RecursiveWork(depth - 1, random) + depth
+            : RecursiveWork(depth - 1, random) - depth;
+    }
+
     [SkippableFact]
     public void Downsampler_ShouldSample_Works()
     {