The growing importance of three-dimensional radiotherapy treatment has been associated with the active presence of advanced computational workflows that can simulate conventional x-ray films from computed tomography (CT) volumetric data to create digitally reconstructed radiographs (DRR). These simulated x-ray images are used to continuously verify the patient alignment in image-guided therapies with 2D-3D image registration. The present DRR rendering pipelines are quite limited to handle huge imaging stacks generated by recent state-of-the-art CT imaging modalities. We present a high performance x-ray rendering pipeline that is capable of generating high quality DRRs from large scale CT volumes. The pipeline is designed to harness the immense computing power of all the heterogeneous computing platforms that are connected to the system relying on OpenCL. Load-balancing optimization is also addressed to equalize the rendering load across the entire system. The performance benchmarks demonstrate the capability of our pipeline to generate high quality DRRs from relatively large CT volumes at interactive frame rates using cost-effective multi-GPU workstations. A 512² DRR frame can be rendered from 1024 × 2048 × 2048 CT volumes at 85 frames per second.