diff --git a/client/src/main/java/org/asynchttpclient/netty/channel/Http2ConnectionState.java b/client/src/main/java/org/asynchttpclient/netty/channel/Http2ConnectionState.java
index 580ab0799..8a7c49064 100644
--- a/client/src/main/java/org/asynchttpclient/netty/channel/Http2ConnectionState.java
+++ b/client/src/main/java/org/asynchttpclient/netty/channel/Http2ConnectionState.java
@@ -129,18 +129,20 @@ public boolean offerPendingOpener(Runnable opener) {
      * Race-free against {@link #failPendingOpeners}: that method sets {@code closed} and drains the queue under
      * {@code pendingLock}. An opener enqueued before the drain runs is caught by the drain; an enqueue attempt
      * sequenced after it observes {@code closed} here (the lock provides the happens-before) and is rejected.
-     * Either way no opener is left stranded.
+     * Either way no opener is left stranded. Opener callbacks always run after releasing {@code pendingLock},
+     * because opening a stream can invoke user code and must not serialize other request submissions.
      *
      * @return {@code true} if the opener was run inline or queued; {@code false} if rejected because the
      *         connection is draining/closed or the pending queue is full (caller must fail the request)
      */
     public boolean offerPendingOpener(NettyResponseFuture<?> future, Runnable opener) {
+        boolean runOpener = false;
         synchronized (pendingLock) {
             if (draining.get() || closed.get()) {
                 return false;
             }
             if (tryAcquireStream()) {
-                opener.run();
+                runOpener = true;
             } else {
                 if (pendingCount >= MAX_PENDING_OPENERS) {
                     return false;
@@ -148,22 +150,35 @@ public boolean offerPendingOpener(NettyResponseFuture<?> future, Runnable opener
                 pendingOpeners.add(new PendingOpener(future, opener));
                 pendingCount++;
             }
-            return true;
         }
+        if (runOpener) {
+            opener.run();
+        }
+        return true;
     }
 
     private void drainPendingOpeners() {
+        List<PendingOpener> ready = null;
         synchronized (pendingLock) {
             // Open as many queued requests as there are now-free stream slots. A single stream completion
             // frees exactly one slot (so this usually runs one opener), but a SETTINGS frame that RAISES
             // SETTINGS_MAX_CONCURRENT_STREAMS frees several at once — drain them all here rather than waking
             // only one and stalling the rest until the next completion (a missed-wakeup; the Issue #2160
             // silent-timeout class). tryAcquireStream() enforces the cap and the draining/closed gate, so
-            // this never over-opens; every poll is under pendingLock, so a non-empty queue always yields a
-            // non-null opener.
+            // this never over-opens; reserve each slot and dequeue its opener atomically under pendingLock.
             while (!pendingOpeners.isEmpty() && tryAcquireStream()) {
                 pendingCount--;
-                pendingOpeners.poll().opener.run();
+                if (ready == null) {
+                    ready = new ArrayList<>();
+                }
+                ready.add(pendingOpeners.poll());
+            }
+        }
+        // Stream opening can invoke user callbacks such as onRequestSend. Run after releasing pendingLock so
+        // a slow callback does not serialize unrelated submissions to this HTTP/2 connection.
+        if (ready != null) {
+            for (PendingOpener pending : ready) {
+                pending.opener.run();
             }
         }
     }
diff --git a/client/src/test/java/org/asynchttpclient/netty/channel/Http2ConnectionStateTest.java b/client/src/test/java/org/asynchttpclient/netty/channel/Http2ConnectionStateTest.java
index ed7a051c2..0c2e6d0b2 100644
--- a/client/src/test/java/org/asynchttpclient/netty/channel/Http2ConnectionStateTest.java
+++ b/client/src/test/java/org/asynchttpclient/netty/channel/Http2ConnectionStateTest.java
@@ -24,6 +24,7 @@
 import java.util.concurrent.CyclicBarrier;
 import java.util.concurrent.ExecutorService;
 import java.util.concurrent.Executors;
+import java.util.concurrent.Future;
 import java.util.concurrent.TimeUnit;
 import java.util.concurrent.atomic.AtomicInteger;
 
@@ -270,6 +271,63 @@ public void pendingOpenerRunsOnRelease() {
         assertEquals(1, executionCount.get(), "Pending opener should have been executed on release");
     }
 
+    @Test
+    public void immediateOpenerRunsOutsidePendingLock() throws Exception {
+        Http2ConnectionState state = new Http2ConnectionState();
+        state.updateMaxConcurrentStreams(2);
+        CountDownLatch openerStarted = new CountDownLatch(1);
+        CountDownLatch releaseOpener = new CountDownLatch(1);
+        ExecutorService executor = Executors.newFixedThreadPool(2);
+
+        try {
+            Future<Boolean> blockingOffer = executor.submit(() ->
+                    state.offerPendingOpener(blockingOpener(openerStarted, releaseOpener)));
+            assertTrue(openerStarted.await(5, TimeUnit.SECONDS), "first opener should start");
+
+            Future<Boolean> competingOffer = executor.submit(() -> state.offerPendingOpener(() -> { }));
+            assertTrue(competingOffer.get(5, TimeUnit.SECONDS),
+                    "a running opener must not hold pendingLock");
+
+            releaseOpener.countDown();
+            assertTrue(blockingOffer.get(5, TimeUnit.SECONDS));
+            state.releaseStream();
+            state.releaseStream();
+        } finally {
+            releaseOpener.countDown();
+            executor.shutdownNow();
+            assertTrue(executor.awaitTermination(5, TimeUnit.SECONDS));
+        }
+    }
+
+    @Test
+    public void queuedOpenerRunsOutsidePendingLock() throws Exception {
+        Http2ConnectionState state = new Http2ConnectionState();
+        state.updateMaxConcurrentStreams(1);
+        assertTrue(state.tryAcquireStream());
+        CountDownLatch openerStarted = new CountDownLatch(1);
+        CountDownLatch releaseOpener = new CountDownLatch(1);
+        state.addPendingOpener(blockingOpener(openerStarted, releaseOpener));
+        ExecutorService executor = Executors.newFixedThreadPool(2);
+
+        try {
+            Future<?> drain = executor.submit(state::releaseStream);
+            assertTrue(openerStarted.await(5, TimeUnit.SECONDS), "queued opener should start");
+
+            Future<Boolean> competingOffer = executor.submit(() -> state.offerPendingOpener(() -> { }));
+            assertTrue(competingOffer.get(5, TimeUnit.SECONDS),
+                    "a drained opener must not hold pendingLock");
+
+            releaseOpener.countDown();
+            drain.get(5, TimeUnit.SECONDS);
+            state.releaseStream();
+            state.releaseStream();
+        } finally {
+            releaseOpener.countDown();
+            executor.shutdownNow();
+            assertTrue(executor.awaitTermination(5, TimeUnit.SECONDS));
+        }
+    }
+
     @Test
     public void multiplePendingOpenersExecuteInOrder() {
         Http2ConnectionState state = new Http2ConnectionState();
@@ -897,4 +955,18 @@ public void releasePermitOnceIsAtomicUnderConcurrency() throws InterruptedExcept
         }
         assertEquals(rounds, totalReleases.get(), "exactly one release per round");
     }
+
+    private static Runnable blockingOpener(CountDownLatch started, CountDownLatch release) {
+        return () -> {
+            started.countDown();
+            try {
+                if (!release.await(10, TimeUnit.SECONDS)) {
+                    throw new AssertionError("timed out waiting to release opener");
+                }
+            } catch (InterruptedException e) {
+                Thread.currentThread().interrupt();
+                throw new AssertionError("interrupted while waiting to release opener", e);
+            }
+        };
+    }
 }