Background: Although surgery is the cornerstone in the treatment of most cases of localized kidney cancer, up to 30% of patients will experience disease recurrence at three years of follow-up. Three RCTs with VEGFR TKIs (ASSURE, PROTECT and ATLAS) failed to demonstrate improvement in disease-free survival (DFS). Only S-TRAC trial showed a significant improvement in DFS, and was approved by the Food and Drug Administration (FDA). However, the matter remains controversial among genitourinary oncologists. Therefore, we performed a meta-analysis to better evaluate the potential benefit of adjuvant VEGFR TKIs after curative intent nephrectomy. Methods: Eligible studies were searched in PubMed databases and limited to phase 3 RCT published from January 1996 to December 2018 of US FDA-approved VEGFR TKIs reporting on patients with RCC treated in the adjuvant setting. A summary hazard-ratio (HR) of disease-free survival (DFS) was calculated using 95% CIs by random-effects or fixed-effects models on the basis of the heterogeneity of included studies. Results: Four RCT (ASSURE, S-TRAC, PROTECT and ATLAS trials) were selected for analysis, including a total of 4,820 patients. A VEGFR TKI (sunitinib, sorafenib, pazopanib or axitinib) was administered in 2,737 patients, and 2,083 received placebo. The summary DFS HR for the overall population was 0.89 (95% CI 0.79-1.00; p = 0.06). When including the report of the ASSURE with the sub-group analysis with high-risk patient population (n = 3,946), the summary HR for DFS was 0.84 (95% CI 0.75-0.95, p = 0,0044). No evidence of publication bias was found. Conclusions: This is the first meta-analysis including the four RCTs in RCC adjuvant setting. This meta-analysis failed to demonstrate improvement in DFS for patients receiving a VEGFR TKI after curative intent nephrectomy. A modest benefit in DFS was observed in a selected sub-group of patients with higher risk for recurrence. There is no data regarding overall survival.