Objective To evaluate the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents for advanced renal cell carcinoma. Methods We searched MEDLINE, EMbase, The Cochrane Library, CBMdisc and China Academic Periodical database from the establishment of each database to April 2009. We included randomized controlled trials (RCTs) that evaluated anti-VEGF agents (sunitinib, sorafenib and bevacizumab). The quality of the included trials was evaluated by two reviewers independently. Meta-analyses were conducted by the Cochrane Collaboration’s RevMan 4.2 software. Results Four RCTs involving 2 320 patients were identified. According to the different interventions for advanced renal cell carcinoma, we divided the patients into two groups: anti-VEGF agents monotherapy and anti-VEGF agents plus interferon combination treatment. Our meta-analyses showed: monotherapy was superior to interferon on inhibition of tumor progression [OR=0.38, 95%CI (0.29, 0.51), Plt;0.01] and control of tumor [OR=2.53, 95%CI (1.87, 3.43), Plt;0.01], but was not significantly different from interferon on the overall effective rate [OR=1.97, 95%CI (0.20, 19.57), P=0.56] and serious side effects [OR=1.98, 95%CI (0.90, 4.34), P=0.09]. There were significant differences between anti-VEGF agents plus interferon and interferon alone on inhibition of tumor progression [OR=0.67, 95%CI (0.53, 0.84), P=0.000 5], overall effective rate [OR=2.65, 95%CI (1.94, 3.61), Plt;0.01], control of tumor [OR=2.14, 95%CI (1.65, 2.78), Plt;0.01] and serious side effects [OR=2.63, 95%CI (2.09, 3.31), Plt;0.01]. Conclusion Compared with interferon, anti-VEGF agents could inhibit tumor progression more effectively. Moreover, the combination therapy with interferon could offer a more favorable overall effective rate for advanced renal cell carcinoma, but then followed by more serious side effects. We need to weigh the merits and demerits of drugs before making a clinical decision for advanced renal cell carcinoma.