Multi-volume visualization is important for displaying relevant information in multimodal or multitemporal medical imaging studies. The main objective with the current study was to develop an efficient GPU-based multi-volume ray caster (MVRC) and validate the proposed visualization system in the context of image-guided surgical navigation. METHODS : Ray casting can produce high-quality 2D images from 3D volume data but the method is computationally demanding, especially when multiple volumes are involved, so a parallel GPU version has been implemented. In the proposed MVRC, imaginary rays are sent through the volumes (one ray for each pixel in the view), and at equal and short intervals along the rays, samples are collected from each volume. Samples from all the volumes are composited using front to back [Formula: see text]-blending. Since all the rays can be processed simultaneously, the MVRC was implemented in parallel on the GPU to achieve acceptable interactive frame rates. The method is fully integrated within the visualization toolkit (VTK) pipeline with the ability to apply different operations (e.g., transformations, clipping, and cropping) on each volume separately. The implemented method is cross-platform (Windows, Linux and Mac OSX) and runs on different graphics card (NVidia and AMD). The speed of the MVRC was tested with one to five volumes of varying sizes: [Formula: see text], and [Formula: see text]. A Tesla C2070 GPU was used, and the output image size was 600 [Formula: see text] 600 pixels. The original VTK single-volume ray caster and the MVRC were compared when rendering only one volume. RESULTS : The multi-volume rendering system achieved an interactive frame rate ([Formula: see text]15 fps) when rendering five small volumes ([Formula: see text] voxels), four medium-sized volumes ([Formula: see text] voxels), and two large volumes ([Formula: see text] voxels). When rendering single volumes, the frame rate of the MVRC was comparable to the original VTK ray caster for small and medium-sized datasets but was approximately 3 frames per second slower for large datasets. The MVRC was successfully integrated in an existing surgical navigation system and was shown to be clinically useful during an ultrasound-guided neurosurgical tumor resection. CONCLUSIONS : A GPU-based MVRC for VTK is a useful tool in medical visualization. The proposed multi-volume GPU-based ray caster for VTK provided high-quality images at reasonable frame rates. The MVRC was effective when used in a neurosurgical navigation application.