diff --git a/src/video_core/renderer_vulkan/vk_graphics_pipeline.cpp b/src/video_core/renderer_vulkan/vk_graphics_pipeline.cpp
index 7c020a012..f43fb572a 100644
--- a/src/video_core/renderer_vulkan/vk_graphics_pipeline.cpp
+++ b/src/video_core/renderer_vulkan/vk_graphics_pipeline.cpp
@@ -109,7 +109,7 @@ GraphicsPipeline::GraphicsPipeline(
 
     const vk::PipelineMultisampleStateCreateInfo multisampling = {
         .rasterizationSamples =
-            LiverpoolToVK::NumSamples(key.num_samples, instance.GetFramebufferSampleCounts()),
+            instance.IsMixedSamplesSupported() ? vk::SampleCountFlagBits::e1 : key.num_samples,
         .sampleShadingEnable = false,
     };
 
@@ -212,7 +212,14 @@ GraphicsPipeline::GraphicsPipeline(
         });
     }
 
+    const vk::AttachmentSampleCountInfoAMD mixed_samples = {
+        .colorAttachmentCount = key.num_color_attachments,
+        .pColorAttachmentSamples = key.color_samples.data(),
+        .depthStencilAttachmentSamples = key.depth_samples,
+    };
+
     const vk::PipelineRenderingCreateInfo pipeline_rendering_ci = {
+        .pNext = instance.IsMixedSamplesSupported() ? &mixed_samples : nullptr,
         .colorAttachmentCount = key.num_color_attachments,
         .pColorAttachmentFormats = key.color_formats.data(),
         .depthAttachmentFormat = key.depth_format,
diff --git a/src/video_core/renderer_vulkan/vk_graphics_pipeline.h b/src/video_core/renderer_vulkan/vk_graphics_pipeline.h
index 59230ae46..b6862df6a 100644
--- a/src/video_core/renderer_vulkan/vk_graphics_pipeline.h
+++ b/src/video_core/renderer_vulkan/vk_graphics_pipeline.h
@@ -39,7 +39,9 @@ struct GraphicsPipelineKey {
     vk::Format depth_format;
     vk::Format stencil_format;
 
-    u32 num_samples;
+    vk::SampleCountFlagBits num_samples;
+    std::array<vk::SampleCountFlagBits, Liverpool::NumColorBuffers> color_samples;
+    vk::SampleCountFlagBits depth_samples;
     u32 mrt_mask;
     AmdGpu::PrimitiveType prim_type;
     Liverpool::PolygonMode polygon_mode;
diff --git a/src/video_core/renderer_vulkan/vk_instance.cpp b/src/video_core/renderer_vulkan/vk_instance.cpp
index 9584329f0..a660f1050 100644
--- a/src/video_core/renderer_vulkan/vk_instance.cpp
+++ b/src/video_core/renderer_vulkan/vk_instance.cpp
@@ -283,6 +283,8 @@ bool Instance::CreateDevice() {
         LOG_INFO(Render_Vulkan, "- shaderImageFloat32AtomicMinMax: {}",
                  shader_atomic_float2_features.shaderImageFloat32AtomicMinMax);
     }
+    nv_framebuffer_mixed_samples = add_extension(VK_NV_FRAMEBUFFER_MIXED_SAMPLES_EXTENSION_NAME);
+    amd_mixed_attachment_samples = add_extension(VK_AMD_MIXED_ATTACHMENT_SAMPLES_EXTENSION_NAME);
     const bool calibrated_timestamps =
         TRACY_GPU_ENABLED ? add_extension(VK_EXT_CALIBRATED_TIMESTAMPS_EXTENSION_NAME) : false;
 
diff --git a/src/video_core/renderer_vulkan/vk_instance.h b/src/video_core/renderer_vulkan/vk_instance.h
index 30848e8b7..6c0f56237 100644
--- a/src/video_core/renderer_vulkan/vk_instance.h
+++ b/src/video_core/renderer_vulkan/vk_instance.h
@@ -171,6 +171,12 @@ public:
         return shader_atomic_float2 && shader_atomic_float2_features.shaderImageFloat32AtomicMinMax;
     }
 
+    /// Returns true if VK_NV_framebuffer_mixed_samples or
+    /// VK_AMD_mixed_attachment_samples is supported
+    bool IsMixedSamplesSupported() const {
+        return nv_framebuffer_mixed_samples || amd_mixed_attachment_samples;
+    }
+
     /// Returns true when geometry shaders are supported by the device
     bool IsGeometryStageSupported() const {
         return features.geometryShader;
@@ -374,6 +380,8 @@ private:
     bool amd_gcn_shader{};
     bool amd_shader_trinary_minmax{};
     bool shader_atomic_float2{};
+    bool nv_framebuffer_mixed_samples{};
+    bool amd_mixed_attachment_samples{};
     bool portability_subset{};
 };
 
diff --git a/src/video_core/renderer_vulkan/vk_pipeline_cache.cpp b/src/video_core/renderer_vulkan/vk_pipeline_cache.cpp
index d7ad47a3c..89ca54585 100644
--- a/src/video_core/renderer_vulkan/vk_pipeline_cache.cpp
+++ b/src/video_core/renderer_vulkan/vk_pipeline_cache.cpp
@@ -278,8 +278,11 @@ bool PipelineCache::RefreshGraphicsKey() {
         vk::FormatFeatureFlagBits2::eDepthStencilAttachment);
     if (regs.depth_buffer.DepthValid()) {
         key.depth_format = depth_format;
+        key.depth_samples = LiverpoolToVK::NumSamples(regs.depth_buffer.NumSamples(),
+                                                      instance.GetFramebufferSampleCounts());
     } else {
         key.depth_format = vk::Format::eUndefined;
+        key.depth_samples = vk::SampleCountFlagBits::e1;
     }
     if (regs.depth_buffer.StencilValid()) {
         key.stencil_format = depth_format;
@@ -290,7 +293,8 @@ bool PipelineCache::RefreshGraphicsKey() {
     key.prim_type = regs.primitive_type;
     key.polygon_mode = regs.polygon_control.PolyMode();
     key.clip_space = regs.clipper_control.clip_space;
-    key.num_samples = regs.NumSamples();
+    key.num_samples =
+        LiverpoolToVK::NumSamples(regs.NumSamples(), instance.GetFramebufferSampleCounts());
 
     const bool skip_cb_binding =
         regs.color_control.mode == AmdGpu::Liverpool::ColorControl::OperationMode::Disable;
@@ -301,6 +305,7 @@ bool PipelineCache::RefreshGraphicsKey() {
     key.num_color_attachments = 0;
     key.color_formats.fill(vk::Format::eUndefined);
     key.color_buffers.fill({});
+    key.color_samples.fill(vk::SampleCountFlagBits::e1);
     key.blend_controls.fill({});
     key.write_masks.fill({});
     key.vertex_buffer_formats.fill(vk::Format::eUndefined);
@@ -335,6 +340,8 @@ bool PipelineCache::RefreshGraphicsKey() {
                                         col_buf.GetDataFmt() == AmdGpu::DataFormat::Format8_8 ||
                                         col_buf.GetDataFmt() == AmdGpu::DataFormat::Format8_8_8_8);
 
+        key.color_samples[remapped_cb] =
+            LiverpoolToVK::NumSamples(col_buf.NumSamples(), instance.GetFramebufferSampleCounts());
         key.color_formats[remapped_cb] =
             LiverpoolToVK::SurfaceFormat(col_buf.GetDataFmt(), col_buf.GetNumberFmt());
         key.color_buffers[remapped_cb] = Shader::PsColorBuffer{