Purpose: The aim of this study was to assess the effects of tyrosine kinase inhibitors (TKIs) following metastasectomy in patients with metastatic renal cell carcinoma (mRCC). Materials and Methods: A systematic search of multiple electronic databases was conducted. The inclusion criteria encompassed randomized clinical trials evaluating the use of TKIs after metastasectomy in mRCC patients. Study outcomes were relapse-free survival (RFS)/disease-free survival (DFS), overall survival (OS), and adverse events of TKIs. Results: Two studies with 197 randomized participants that compared TKIs following metastasectomy versus metastasectomy alone were identified. According to these studies, TKIs following metastasectomy may result in little to no difference in RFS/DFS (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.65?1.57; I 2 =29%; low-certainty evidence). TKIs after metastasectomy may slightly increase OS, but the CI crossed the line of no effect (HR, 0.80; 95% CI, 0.06?9.87; I2 =86%; low-certainty evidence). TKIs after metastasectomy likely resulted in a large increase in adverse events (risk ratio, 2.76; 95% CI: 1.65?4.62; I2 =not applicable; moderatecertainty evidence). Conclusions: TKIs following metastasectomy did not improve RFS/DFS, but slightly improved OS. It ...