214 Background: Sunitinib, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, has been approved in adjuvant treatment of high risk renal cell carcinoma (RCC) after nephrectomy despite distinct results among studies, along with notable safety concerns. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of grade 3 and 4 adverse events in patients treated with adjuvant sunitinib. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase 3 RCTs which utilized adjuvant sunitinib in high risk RCC after nephrectomy were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Two phase III RCTs with a total of 1866 patients were eligible. Studies utilized sunitinib versus placebo. The randomization ratio was 1:1 in both ASSURE and S-TRAC studies. The RR of high-grade adverse effects were as follows: hypertension, 4.26 (95% CI: 2.89 – 6.26, p < 0.001); fatigue, 5.40 (95% CI: 3.49 – 8.34; p < 0.001); rash/desquamation, 5.00 (95% CI: 1.59 – 15.68; p = 0.006); hand foot syndrome, 18.68 (95% CI: 5.98 – 58.28, p < 0.001); asthenia, 6.57 (95% CI: 1.005 – 43.04; p = 0.049); diarrhea, 18.08 (95% CI: 6.63 – 49.32; p < 0.001); dyspepsia, 12.68 (95% CI: 2.40 – 66.80, p = 0.003); stomatitis, 29.15 (95% CI: 5.73 – 148.18; p < 0.001); nausea, 19.63 (95% CI: 3.81 – 100.97; p < 0.001); and vomiting, 8.21 (95% CI: 2.21 – 30.51; p = 0.002). Conclusions: The rate of high-grade hypertension, fatigue, asthenia, dermatological toxicities, including hand foot syndrome, and gastrointestinal toxicities were extremely high in patients treated with adjuvant sunitinib, compared to placebo arm. Fatigue, hand foot syndrome and gastrointestinal toxicities significantly contribute to patients’ quality of life and providing good supportive care is warranted.