Background: Increasing evidence suggests that angiotensin II modulates angiogenesis and tumorigenesis. In this study, we utilized a clinical trials database to evaluate the role of ASIs (angiotensin-converting enzyme inhibitors and angiotension-receptor blockers) on survival outcomes in pts with mRCC. Methods: We conducted an analysis of pts with mRCC treated from 2003-2013 on phase III (NCT00083889, NCT00065468, NCT00678392, NCT00474786, NCT00631371, NCT00920816) and II clinical trials (NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00835978). We evaluated pts treated with ASIs at baseline or within the first 30 days of study. Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results: We identified 4,736 pts treated with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (TEM) (n=457), TEM + interferon-alfa (IFN-α) (n=208), bevacizumab (BEV) + TEM (n=393), BEV + IFN-α (n=391), or IFN-α (n=560). Most pts were < 65 years of age (69%), male (71%), with clear-cell histology (89%) and prior nephrectomy (70%). With regard to International mRCC Database Consortium risk groups, 14%, 42%, and 24% had favorable, intermediate, and poor-risk disease, respectively. 1383 (29%) pts received treatment with an ASI. Baseline hypertension was present in 84% of ASI users and 33% of ASI non-users. ASI use was associated with improved progression-free survival (PFS) and overall survival (OS) when compared to pts who did not receive an ASI (Table). This association was retained in multivariable analysis adjusted for age, gender, presence of bone metastases, and risk groups. Conclusions: This is the largest retrospective study to date evaluating the role of ASIs on outcomes in cancer pts. In this analysis, we demonstrate that concomitant use of ASIs may improve survival outcomes in pts with mRCC treated in the era of targeted therapy.