diff --git a/extensions/resteasy-reactive/quarkus-resteasy-reactive-common/deployment/src/main/java/io/quarkus/resteasy/reactive/common/deployment/ResteasyReactiveCommonProcessor.java b/extensions/resteasy-reactive/quarkus-resteasy-reactive-common/deployment/src/main/java/io/quarkus/resteasy/reactive/common/deployment/ResteasyReactiveCommonProcessor.java
index 74c2e9f840639..4812b57c2f46e 100644
--- a/extensions/resteasy-reactive/quarkus-resteasy-reactive-common/deployment/src/main/java/io/quarkus/resteasy/reactive/common/deployment/ResteasyReactiveCommonProcessor.java
+++ b/extensions/resteasy-reactive/quarkus-resteasy-reactive-common/deployment/src/main/java/io/quarkus/resteasy/reactive/common/deployment/ResteasyReactiveCommonProcessor.java
@@ -327,7 +327,7 @@ void deprioritizeLegacyProviders(BuildProducer<MessageBodyReaderOverrideBuildIte
      * @param buildTimeConditions the build time conditions from which the excluded classes are extracted.
      * @return the set of classes that have been annotated with unsuccessful build time conditions.
      */
-    private static Set<String> getExcludedClasses(List<BuildTimeConditionBuildItem> buildTimeConditions) {
+    public static Set<String> getExcludedClasses(List<BuildTimeConditionBuildItem> buildTimeConditions) {
         return buildTimeConditions.stream()
                 .filter(item -> !item.isEnabled())
                 .map(BuildTimeConditionBuildItem::getTarget)
diff --git a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/main/java/io/quarkus/resteasy/reactive/server/deployment/ResteasyReactiveProcessor.java b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/main/java/io/quarkus/resteasy/reactive/server/deployment/ResteasyReactiveProcessor.java
index cb06597935f48..5548d55c5ab86 100644
--- a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/main/java/io/quarkus/resteasy/reactive/server/deployment/ResteasyReactiveProcessor.java
+++ b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/main/java/io/quarkus/resteasy/reactive/server/deployment/ResteasyReactiveProcessor.java
@@ -756,7 +756,7 @@ public void setupDeployment(BeanArchiveIndexBuildItem beanArchiveIndexBuildItem,
         BeanFactory<ResteasyReactiveInitialiser> initClassFactory = recorder.factory(QUARKUS_INIT_CLASS,
                 beanContainerBuildItem.getValue());
 
-        String applicationPath = determineApplicationPath(index, getAppPath(serverConfig.path));
+        String applicationPath = determineApplicationPath(appResult, getAppPath(serverConfig.path));
         // spec allows the path contain encoded characters
         if ((applicationPath != null) && applicationPath.contains("%")) {
             applicationPath = Encode.decodePath(applicationPath);
@@ -981,32 +981,19 @@ private Optional<String> getAppPath(Optional<String> newPropertyValue) {
         return newPropertyValue;
     }
 
-    private String determineApplicationPath(IndexView index, Optional<String> defaultPath) {
-        Collection<AnnotationInstance> applicationPaths = index.getAnnotations(ResteasyReactiveDotNames.APPLICATION_PATH);
-        if (applicationPaths.isEmpty()) {
+    private String determineApplicationPath(ApplicationScanningResult appResult,
+            Optional<String> defaultPath) {
+        if (appResult.getSelectedAppClass() == null) {
             return defaultPath.orElse("/");
         }
-        // currently we only examine the first class that is annotated with @ApplicationPath so best
-        // fail if the user code has multiple such annotations instead of surprising the user
-        // at runtime
-        if (applicationPaths.size() > 1) {
-            StringBuilder sb = new StringBuilder();
-            boolean first = true;
-            for (AnnotationInstance annotationInstance : applicationPaths) {
-                if (first) {
-                    first = false;
-                } else {
-                    sb.append(",");
-                }
-                sb.append(annotationInstance.target().asClass().name().toString());
-            }
-            throw new RuntimeException("Multiple classes ( " + sb.toString()
-                    + ") have been annotated with @ApplicationPath which is currently not supported");
+        AnnotationInstance applicationPathValue = appResult.getSelectedAppClass()
+                .classAnnotation(ResteasyReactiveDotNames.APPLICATION_PATH);
+        if (applicationPathValue == null) {
+            return defaultPath.orElse("/");
         }
         String applicationPath = null;
-        AnnotationValue applicationPathValue = applicationPaths.iterator().next().value();
-        if ((applicationPathValue != null)) {
-            applicationPath = applicationPathValue.asString();
+        if ((applicationPathValue.value() != null)) {
+            applicationPath = applicationPathValue.value().asString();
         }
         return applicationPath;
     }
diff --git a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/MultipleApplicationClassesWithBuildProfileTest.java b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/MultipleApplicationClassesWithBuildProfileTest.java
new file mode 100644
index 0000000000000..3db55b97b2326
--- /dev/null
+++ b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/MultipleApplicationClassesWithBuildProfileTest.java
@@ -0,0 +1,52 @@
+package io.quarkus.resteasy.reactive.server.test;
+
+import static io.restassured.RestAssured.get;
+
+import javax.ws.rs.ApplicationPath;
+import javax.ws.rs.GET;
+import javax.ws.rs.Path;
+import javax.ws.rs.core.Application;
+
+import org.hamcrest.Matchers;
+import org.junit.jupiter.api.Test;
+import org.junit.jupiter.api.extension.RegisterExtension;
+
+import io.quarkus.arc.properties.IfBuildProperty;
+import io.quarkus.test.QuarkusUnitTest;
+
+class MultipleApplicationClassesWithBuildProfileTest {
+
+    @RegisterExtension
+    static QuarkusUnitTest runner = new QuarkusUnitTest()
+            .withApplicationRoot((jar) -> jar
+                    .addClasses(
+                            Application1.class, Application2.class, TestResource.class));
+
+    @Test
+    public void testNoAnnotation() {
+        get("/1/test")
+                .then()
+                .statusCode(200)
+                .body(Matchers.equalTo("test"));
+    }
+
+    @ApplicationPath("1")
+    public static class Application1 extends Application {
+
+    }
+
+    @ApplicationPath("2")
+    @IfBuildProperty(name = "some.prop2", stringValue = "v2")
+    public static class Application2 extends Application {
+
+    }
+
+    @Path("test")
+    public static class TestResource {
+
+        @GET
+        public String get() {
+            return "test";
+        }
+    }
+}
diff --git a/independent-projects/resteasy-reactive/common/processor/src/main/java/org/jboss/resteasy/reactive/common/processor/scanning/ResteasyReactiveScanner.java b/independent-projects/resteasy-reactive/common/processor/src/main/java/org/jboss/resteasy/reactive/common/processor/scanning/ResteasyReactiveScanner.java
index a3ac1781dbad2..cefc3375a9f7c 100644
--- a/independent-projects/resteasy-reactive/common/processor/src/main/java/org/jboss/resteasy/reactive/common/processor/scanning/ResteasyReactiveScanner.java
+++ b/independent-projects/resteasy-reactive/common/processor/src/main/java/org/jboss/resteasy/reactive/common/processor/scanning/ResteasyReactiveScanner.java
@@ -80,6 +80,9 @@ public static ApplicationScanningResult scanForApplicationClass(IndexView index,
             if (Modifier.isAbstract(applicationClassInfo.flags())) {
                 continue;
             }
+            if (excludedClasses.contains(applicationClassInfo.name().toString())) {
+                continue;
+            }
             if (selectedAppClass != null) {
                 throw new RuntimeException("More than one Application class: " + applications);
             }