diff --git a/packages/calcite-components/src/components/tooltip/TooltipManager.ts b/packages/calcite-components/src/components/tooltip/TooltipManager.ts
index 5ee59a8df6b..302841ebb1e 100644
--- a/packages/calcite-components/src/components/tooltip/TooltipManager.ts
+++ b/packages/calcite-components/src/components/tooltip/TooltipManager.ts
@@ -148,6 +148,11 @@ export default class TooltipManager {
     const composedPath = event.composedPath();
     const tooltip = this.queryTooltip(composedPath);
 
+    if (this.pathHasOpenTooltip(tooltip, composedPath)) {
+      this.clearHoverTimeout();
+      return;
+    }
+
     this.closeTooltipIfNotActive(tooltip);
 
     if (!tooltip) {
diff --git a/packages/calcite-components/src/components/tooltip/tooltip.e2e.ts b/packages/calcite-components/src/components/tooltip/tooltip.e2e.ts
index cf8d0c4b271..ba6e2a67b46 100644
--- a/packages/calcite-components/src/components/tooltip/tooltip.e2e.ts
+++ b/packages/calcite-components/src/components/tooltip/tooltip.e2e.ts
@@ -1127,7 +1127,7 @@ describe("calcite-tooltip", () => {
 
   describe("allows clicking on an open tooltip", () => {
     const pageContent = html`
-      <calcite-tooltip placement="auto" reference-element="ref">content</calcite-tooltip>
+      <calcite-tooltip placement="auto" reference-element="ref">content <button>test</button></calcite-tooltip>
       <button id="ref">referenceElement</button>
       <button id="other">other</button>
     `;
@@ -1147,6 +1147,11 @@ describe("calcite-tooltip", () => {
       await page.waitForChanges();
       expect(await tooltip.getProperty("open")).toBe(true);
 
+      const button = await page.find("button");
+      await button.click();
+      await page.waitForChanges();
+      expect(await tooltip.getProperty("open")).toBe(true);
+
       await dispatchClickEvent(page, "#other");
       expect(await tooltip.getProperty("open")).toBe(false);
     });
@@ -1166,6 +1171,11 @@ describe("calcite-tooltip", () => {
       await page.waitForChanges();
       expect(await tooltip.getProperty("open")).toBe(true);
 
+      const button = await page.find("button");
+      await button.focus();
+      await page.waitForChanges();
+      expect(await tooltip.getProperty("open")).toBe(true);
+
       const other = await page.find("#other");
       await other.focus();
       await page.waitForChanges();
diff --git a/packages/calcite-components/src/components/tooltip/tooltip.stories.ts b/packages/calcite-components/src/components/tooltip/tooltip.stories.ts
index 4f62fbd4a2c..eeedd5f1bd4 100644
--- a/packages/calcite-components/src/components/tooltip/tooltip.stories.ts
+++ b/packages/calcite-components/src/components/tooltip/tooltip.stories.ts
@@ -1,6 +1,7 @@
 import { html } from "../../../support/formatting";
 import { placements } from "../../utils/floating-ui";
 import { boolean, modesDarkDefault } from "../../../.storybook/utils";
+import { placeholderImage } from "../../../.storybook/placeholderImage";
 import { Tooltip } from "./tooltip";
 
 const contentHTML = `Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua`;
@@ -93,3 +94,11 @@ export const transparentBG_TestOnly = (): string => html`
     <calcite-tooltip reference-element="reference-element" placement="auto" open> ${contentHTML} </calcite-tooltip>
   </div>
 `;
+
+export const withInteractiveContent = (): string =>
+  html`<div style="width: 400px;">
+    ${referenceElementHTML}
+    <calcite-tooltip reference-element="reference-element" placement="auto" open
+      ><img width="100%" src="${placeholderImage({ width: 360, height: 90 })}" /> <p>${contentHTML}</p> <calcite-button>Click me</calcite-button
+    </calcite-tooltip>
+  </div>`;