Abstract Background As genome sequencing becomes better integrated into scientific research, government policy, and personalized medicine, the primary challenge for researchers is shifting from generating raw data to analyzing these vast datasets. Although much work has been done to reduce compute times using various configurations of traditional CPU computing infrastructures, Graphics Processing Units (GPUs) offer opportunities to accelerate genomic workflows by orders of magnitude. Here we benchmark one GPU-accelerated software suite called NVIDIA Parabricks on Amazon Web Services (AWS), Google Cloud Platform (GCP), and an NVIDIA DGX cluster. We benchmarked six variant calling pipelines, including two germline callers (HaplotypeCaller and DeepVariant) and four somatic callers (Mutect2, Muse, LoFreq, SomaticSniper). Results We achieved up to 65 × acceleration with germline variant callers, bringing HaplotypeCaller runtimes down from 36 h to 33 min on AWS, 35 min on GCP, and 24 min on the NVIDIA DGX. Somatic callers exhibited more variation between the number of GPUs and computing platforms. On cloud platforms, GPU-accelerated germline callers resulted in cost savings compared with CPU runs, whereas some somatic callers were more expensive than CPU runs because their GPU acceleration was not sufficient to overcome the increased GPU cost. Conclusions Germline variant callers scaled well with the number of GPUs across platforms, whereas somatic variant callers exhibited more variation in the number of GPUs with the fastest runtimes, suggesting that, at least with the version of Parabricks used here, these workflows are less GPU optimized and require benchmarking on the platform of choice before being deployed at production scales. Our study demonstrates that GPUs can be used to greatly accelerate genomic workflows, thus bringing closer to grasp urgent societal advances in the areas of biosurveillance and personalized medicine.