diff --git a/res/css/views/messages/_MessageActionBar.scss b/res/css/views/messages/_MessageActionBar.scss
index a9c6e3b39c..ab434d8286 100644
--- a/res/css/views/messages/_MessageActionBar.scss
+++ b/res/css/views/messages/_MessageActionBar.scss
@@ -65,6 +65,12 @@ limitations under the License.
 .mx_MessageActionBar_maskButton {
     width: 28px;
     height: 28px;
+
+    &:disabled,
+    &[disabled] {
+        cursor: not-allowed;
+        opacity: .75;
+    }
 }
 
 .mx_MessageActionBar_maskButton::after {
diff --git a/src/components/views/messages/MessageActionBar.tsx b/src/components/views/messages/MessageActionBar.tsx
index 9ceed42038..81b014607b 100644
--- a/src/components/views/messages/MessageActionBar.tsx
+++ b/src/components/views/messages/MessageActionBar.tsx
@@ -19,7 +19,7 @@ limitations under the License.
 import React, { ReactElement, useEffect } from 'react';
 import { EventStatus, MatrixEvent, MatrixEventEvent } from 'matrix-js-sdk/src/models/event';
 import classNames from 'classnames';
-import { MsgType } from 'matrix-js-sdk/src/@types/event';
+import { MsgType, RelationType } from 'matrix-js-sdk/src/@types/event';
 
 import type { Relations } from 'matrix-js-sdk/src/models/relations';
 import { _t } from '../../../languageHandler';
@@ -166,7 +166,7 @@ interface IMessageActionBarProps {
     isQuoteExpanded?: boolean;
     getRelationsForEvent?: (
         eventId: string,
-        relationType: string,
+        relationType: RelationType | string,
         eventType: string
     ) => Relations;
 }
@@ -303,11 +303,19 @@ export default class MessageActionBar extends React.PureComponent<IMessageAction
             key="cancel"
         />;
 
+        const hasARelation = !!this.props.mxEvent?.getRelation()?.rel_type;
+
         const threadTooltipButton = <CardContext.Consumer key="thread">
             { context =>
                 <RovingAccessibleTooltipButton
                     className="mx_MessageActionBar_maskButton mx_MessageActionBar_threadButton"
-                    title={_t("Reply in thread")}
+
+                    disabled={hasARelation}
+                    title={!hasARelation
+                        ? _t("Reply in thread")
+                        : _t("Can't create a thread from an event with an existing relation")
+                    }
+
                     onClick={this.onThreadClick.bind(null, context.isCard)}
                 />
             }
diff --git a/src/i18n/strings/en_EN.json b/src/i18n/strings/en_EN.json
index 9743cc028f..8249025ad2 100644
--- a/src/i18n/strings/en_EN.json
+++ b/src/i18n/strings/en_EN.json
@@ -2103,6 +2103,7 @@
     "React": "React",
     "Edit": "Edit",
     "Reply in thread": "Reply in thread",
+    "Can't create a thread from an event with an existing relation": "Can't create a thread from an event with an existing relation",
     "Reply": "Reply",
     "Collapse quotes": "Collapse quotes",
     "Expand quotes": "Expand quotes",