diff --git a/CHANGES.txt b/CHANGES.txt
index 22818c9313e8..b9d4aa1fc902 100644
--- a/CHANGES.txt
+++ b/CHANGES.txt
@@ -1,4 +1,5 @@
 4.0.1
+ * Harden PrunableArrayQueue against Pruner implementations that might throw exceptions (CASSANDRA-16866)
  * Move RepairedDataInfo to the execution controller rather than the ReadCommand to avoid unintended sharing (CASSANDRA-16721)
  * Bump zstd-jni version to 1.5.0-4 (CASSANDRA-16884)
  * Remove assumption that all urgent messages are small (CASSANDRA-16877)
diff --git a/src/java/org/apache/cassandra/net/PrunableArrayQueue.java b/src/java/org/apache/cassandra/net/PrunableArrayQueue.java
index 1fca43ca2b33..9c91ca71255c 100644
--- a/src/java/org/apache/cassandra/net/PrunableArrayQueue.java
+++ b/src/java/org/apache/cassandra/net/PrunableArrayQueue.java
@@ -19,6 +19,8 @@
 
 import java.util.function.Predicate;
 
+import org.apache.cassandra.utils.Throwables;
+
 /**
  * A growing array-based queue that allows efficient bulk in-place removal.
  *
@@ -103,10 +105,12 @@ boolean isEmpty()
      *
      * @return count of removed elements.
      */
+    @SuppressWarnings("ThrowFromFinallyBlock")
     int prune(Pruner<E> pruner)
     {
         E e;
         int removed = 0;
+        Throwable error = null;
 
         try
         {
@@ -120,11 +124,35 @@ int prune(Pruner<E> pruner)
                 int k = (tail - 1 - i) & mask;
                 e = buffer[k];
 
-                if (pruner.shouldPrune(e))
+                boolean shouldPrune = false;
+
+                // If any error has been thrown from the Pruner callbacks, don't bother asking the
+                // pruner. Just move any elements that need to be moved, correct the head, and rethrow.
+                if (error == null)
+                {
+                    try
+                    {
+                        shouldPrune = pruner.shouldPrune(e);
+                    }
+                    catch (Throwable t)
+                    {
+                        error = t;
+                    }
+                }
+
+                if (shouldPrune)
                 {
                     buffer[k] = null;
                     removed++;
-                    pruner.onPruned(e);
+
+                    try
+                    {
+                        pruner.onPruned(e);
+                    }
+                    catch (Throwable t)
+                    {
+                        error = t;
+                    }
                 }
                 else
                 {
@@ -133,13 +161,28 @@ int prune(Pruner<E> pruner)
                         buffer[(k + removed) & mask] = e;
                         buffer[k] = null;
                     }
-                    pruner.onKept(e);
+
+                    try
+                    {
+                        pruner.onKept(e);
+                    }
+                    catch (Throwable t)
+                    {
+                        if (error == null)
+                        {
+                            error = t;
+                        }
+                    }
                 }
             }
         }
         finally
         {
             head = (head + removed) & mask;
+
+            // Rethrow any error(s) from the Pruner callbacks, but only after the queue state is valid.
+            if (error != null)
+                throw Throwables.unchecked(error);
         }
 
         return removed;
diff --git a/test/unit/org/apache/cassandra/net/PrunableArrayQueueTest.java b/test/unit/org/apache/cassandra/net/PrunableArrayQueueTest.java
index c4fd55a8aa27..34f61a611498 100644
--- a/test/unit/org/apache/cassandra/net/PrunableArrayQueueTest.java
+++ b/test/unit/org/apache/cassandra/net/PrunableArrayQueueTest.java
@@ -17,14 +17,21 @@
  */
 package org.apache.cassandra.net;
 
+import java.util.Random;
+
 import org.junit.Test;
 
+import org.slf4j.Logger;
+import org.slf4j.LoggerFactory;
+
 import org.apache.cassandra.net.PrunableArrayQueue;
 
 import static org.junit.Assert.*;
 
 public class PrunableArrayQueueTest
 {
+    private static final Logger logger = LoggerFactory.getLogger(PrunableArrayQueueTest.class);
+
     private final PrunableArrayQueue<Integer> queue = new PrunableArrayQueue<>(8);
 
     @Test
@@ -127,4 +134,70 @@ public void onKept(Integer val)
             assertEquals((Integer) i, queue.poll());
         assertTrue(queue.isEmpty());
     }
+
+    @Test
+    public void testUnreliablePruner()
+    {
+        long seed = System.currentTimeMillis();
+        Random rand = new Random(seed);
+
+        logger.info("Testing unreliable pruner with random seed {}...", seed);
+
+        int iteratons = 100;
+        int startingQueueSize = 1024;
+        double pruneChance = 0.1;
+        double errorOnKeptChance = 0.00005;
+        double errorOnPruneChance = 0.00002;
+
+        for (int i = 0; i < iteratons; i++)
+        {
+            int failureValue = rand.nextInt(startingQueueSize);
+
+            PrunableArrayQueue<Integer> testQueue = new PrunableArrayQueue<>(startingQueueSize);
+
+            for (int o = 0; o < startingQueueSize; o++)
+                testQueue.offer(o);
+
+            class UnreliablePruner implements PrunableArrayQueue.Pruner<Integer>
+            {
+                public boolean shouldPrune(Integer value)
+                {
+                    if (rand.nextDouble() < errorOnPruneChance)
+                        throw new RuntimeException("Failed on pruning check for value: " + value);
+
+                    return rand.nextDouble() < pruneChance;
+                }
+
+                public void onPruned(Integer value)
+                {
+                    if (value == failureValue)
+                        throw new RuntimeException("Failed on pruned value: " + value);
+                }
+
+                public void onKept(Integer value)
+                {
+                    if (rand.nextDouble() < errorOnKeptChance)
+                        throw new RuntimeException("Failed on retained value: " + value);
+                }
+            }
+
+            assertEquals(startingQueueSize, testQueue.size());
+
+            try
+            {
+                testQueue.prune(new UnreliablePruner());
+            }
+            catch (RuntimeException e)
+            {
+                logger.info("Expected pruning failure with seed {}", seed, e);
+            }
+
+            for (int p = 0, postPruneSize = testQueue.size(); p < postPruneSize; p++)
+            {
+                assertNotNull("Queue should contain no null elements after pruning. Seed: " + seed + ". Iteration: " + i, testQueue.poll());
+            }
+
+            assertEquals("Queue size should be zero after draining. Seed: " + seed + ". Iteration: " + i, 0, testQueue.size());
+        }
+    }
 }
\ No newline at end of file