diff --git a/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusMainTestExtension.java b/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusMainTestExtension.java
index 95c90923c412e..aeb551a1cd7b7 100644
--- a/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusMainTestExtension.java
+++ b/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusMainTestExtension.java
@@ -64,13 +64,18 @@ private void ensurePrepared(ExtensionContext extensionContext, Class<? extends Q
             throws Exception {
         JBossVersion.disableVersionLogging();
 
+        boolean mixedWithQuarkusTest = false;
         ExtensionContext.Store store = extensionContext.getStore(ExtensionContext.Namespace.GLOBAL);
         Class<?> testType = store.get(IO_QUARKUS_TESTING_TYPE, Class.class);
         if (testType != null) {
             if (testType != QuarkusMainTest.class) {
-                throw new IllegalStateException(
-                        "Cannot mix both @QuarkusMainTest based tests and " + testType.getName()
-                                + " based tests in the same run");
+                if (testType.equals(QuarkusTest.class)) {
+                    mixedWithQuarkusTest = true;
+                } else {
+                    throw new IllegalStateException(
+                            "Cannot mix both @QuarkusMainTest based tests and " + testType.getName()
+                                    + " based tests in the same run");
+                }
             }
         } else {
             store.put(IO_QUARKUS_TESTING_TYPE, QuarkusMainTest.class);
@@ -78,7 +83,7 @@ private void ensurePrepared(ExtensionContext extensionContext, Class<? extends Q
 
         QuarkusTestExtension.ExtensionState state = store.get(QuarkusTestExtension.ExtensionState.class.getName(),
                 QuarkusTestExtension.ExtensionState.class);
-        boolean wrongProfile = !Objects.equals(profile, quarkusTestProfile);
+        boolean wrongProfile = !Objects.equals(profile, quarkusTestProfile) || mixedWithQuarkusTest;
         // we reload the test resources if we changed test class and if we had or will have per-test test resources
         boolean reloadTestResources = !Objects.equals(extensionContext.getRequiredTestClass(), currentJUnitTestClass)
                 && (hasPerTestResources || hasPerTestResources(extensionContext));
diff --git a/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusTestExtension.java b/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusTestExtension.java
index 676d898885208..ae0e3f9e4dd43 100644
--- a/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusTestExtension.java
+++ b/test-framework/junit5/src/main/java/io/quarkus/test/junit/QuarkusTestExtension.java
@@ -106,6 +106,7 @@
 import io.quarkus.test.junit.callback.QuarkusTestMethodContext;
 import io.quarkus.test.junit.internal.DeepClone;
 import io.quarkus.test.junit.internal.SerializationWithXStreamFallbackDeepClone;
+import io.quarkus.test.junit.main.QuarkusMainTest;
 
 public class QuarkusTestExtension extends AbstractJvmQuarkusTestExtension
         implements BeforeEachCallback, BeforeTestExecutionCallback, AfterTestExecutionCallback, AfterEachCallback,
@@ -569,19 +570,25 @@ private boolean isNativeOrIntegrationTest(Class<?> clazz) {
     }
 
     private QuarkusTestExtensionState ensureStarted(ExtensionContext extensionContext) {
+        boolean mixedWithQuarkusMainTest = false;
         ExtensionContext.Store store = getStoreFromContext(extensionContext);
         Class<?> testType = store.get(IO_QUARKUS_TESTING_TYPE, Class.class);
         if (testType != null) {
             if (testType != QuarkusTest.class) {
-                throw new IllegalStateException(
-                        "Cannot mix both @QuarkusTest based tests and " + testType.getName() + " based tests in the same run");
+                if (testType.equals(QuarkusMainTest.class)) {
+                    mixedWithQuarkusMainTest = true;
+                } else {
+                    throw new IllegalStateException(
+                            "Cannot mix both @QuarkusTest based tests and " + testType.getName()
+                                    + " based tests in the same run");
+                }
             }
         } else {
             store.put(IO_QUARKUS_TESTING_TYPE, QuarkusTest.class);
         }
         QuarkusTestExtensionState state = getState(extensionContext);
         Class<? extends QuarkusTestProfile> selectedProfile = getQuarkusTestProfile(extensionContext);
-        boolean wrongProfile = !Objects.equals(selectedProfile, quarkusTestProfile);
+        boolean wrongProfile = !Objects.equals(selectedProfile, quarkusTestProfile) || mixedWithQuarkusMainTest;
         // we reload the test resources if we changed test class and the new test class is not a nested class, and if we had or will have per-test test resources
         boolean reloadTestResources = !Objects.equals(extensionContext.getRequiredTestClass(), currentJUnitTestClass)
                 && !isNested(currentJUnitTestClass, extensionContext.getRequiredTestClass())