Background: A growing body of evidence has demonstrated the antineoplastic activity of statins. The objective of this study was to investigate the impact of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era. Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for age, sex, race, histology, prior therapy, body-mass index, and other known prognostic factors and the Kaplan-Meier method. Results: We identified 4,736 patients treated with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (n=457), temsirolimus + interferon-alpha (n=208), bevacizumab + temsirolimus (n=393), bevacizumab + interferon-alpha (n=391), or interferon-alpha (n=560), of whom 511 were statin users. Overall, statin users demonstrated a statistically significant improvement in overall survival (OS) but not progression-free survival (PFS) compared to non-users (OS: 25.6 versus 18.9 months; p=0.015; adjusted hazard ratio [aHR] 0.787; 95% CI, 0.648-0.955; PFS: 7.9 versus 6.9 months; p=0.823, aHR 1.018; 95% CI, 0.867-1.196). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, p=0.023; aHR 0.749; 95% CI, 0.584-0.961) or mammalian target of rapamycin (18.6 versus 14.0; p=0.035; aHR 0.657; 95% CI, 0.445-0.972), but not in those receiving interferon-alpha (15.6 versus 14.8 months; p=0.410; aHR 1.292; 95% CI 0.703-2.275). Adverse events were similar between statin users and non-users. Conclusions: In the largest RCC analysis to date, we demonstrate that statin use improved survival outcomes in patients with mRCC treated in the targeted therapy era. Statins could represents a potential adjunct therapeutic option for patients with metastatic RCC; however, this hypothesis needs to be corroborated with preclinical work exploring the mechanisms underlying their anti-cancer effects and well-designed clinical trials investigating the clinical benefits of adding statins to modern therapies.