Background: Tivozanib is a potent and highly selective VEGF receptor (R) tyrosine kinase inhibitor in clinical development for mRCC. Methods: The TIVO-3 study enrolled subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI, stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized 1:1 to T or sorafenib. Tivozanib demonstrated PFS and ORR advantages over sorafenib. Here we report long term durability of response based on investigator assessment and updated overall survival. Results: There were 41 responders (23%) to tivozanib and 20 responders (11%) to sorafenib. The median duration of response (mDoR) was 20.3 months (95% CI: 9.8, 29.9) and 9.0 months (95% CI: 3.7, 16.6) for tivozanib and sorafenib, respectively. With prolonged follow up there were 270 deaths; the HR for overall survival favored tivozanib at 0.91 (95% CI: 0.716, 1.165). Clinical trial information: NCT02627963. Conclusions: Tivozanib treatment in third and fourth line mRCC results in longer PFS, higher objective response rate and more durable responses compared to sorafenib. There is no difference in overall survival.