In a joint collaboration, Oxford Biomedica and Repligen increased the yield of viral vectors from suspension-cultured bioreactors several fold using tangential-flow depth filtration (TFDF). The yield for a single clarification step was 95% as compared to 70% by standard depth filtration. The TFDF tubular format and low shear enabled further yield increases through multiple harvests from the same seeding. A single seeded bioreactor produced two harvests of 95% and 85%. The 180% yield represents a 2.5-fold increase over a single depth-filtration harvest at 70%. The process was shown to scale from 5 L to 50 L with an average flux of 750 LMH and three different lentiviral model systems, demonstrating broad applicability. Logistics and execution required a single filter, three AseptiQuik connections, and typically 15–20 minutes for setup and breakdown, resulting in a four-fold reduction in required footprint as compared to conventional depth filtration.