Circulating tumor DNA (ctDNA) from a liquid biopsy allows for the non-invasive, real-time assessment of a tumor for cancer patients before and after treatment, which could overcome tissue limitations such as insufficient quantity and tumor heterogeneity. Ultra-deep sequencing and unique molecular identifiers (UMI) are required to detect low frequency tumor derived variants. For liquid biopsy to become standard of care, researchers will need to further establish clinical utility and demonstrate a clinically appropriate turnaround time for analyzing the deep sequencing data. The TruSightTM Oncology 500 (TSO500) ctDNA assay (Illumina, San Diego CA; Research Use Only) includes a data analysis solution that enables researchers to perform ultra-fast and accurate variant detection in liquid biopsies. Here we present a comparison of performance with our standard in-house bioinformatics analysis against the newly develop DRAGEN™ Bio-IT platform.