INTRODUCTION: Given the lack of comparative studies on adjuvant treatment for clear cell renal cell carcinoma, we present an updated systematic review, exploring the various options for adjuvant therapy. This review is conducted in accordance with the PRISMA guidelines. MATERIAL AND METHOD: A systematic review was conducted, and 13 clinical trials were included after applying the pre-specified inclusion criteria. The risk of bias and the level of evidence were assessed. Subsequently, the requisite data were extracted in order to present the findings of the studies. RESULTS AND DISCUSSION: The present systematic review establishes that pembrolizumab can be used as adjuvant therapy in patients with advanced renal cancer at high risk after nephrectomy. This is supported by the KEYNOTE-564 study, which concluded that it increased disease-free survival (DFS) and overall survival (OS). The use of sunitinib is discussed, since the study published in NEJM shows a modest benefit in terms of DFS, but only in an independent and blinded central review. According to the PROTECT study, pazopanib has no overall benefit. The EVEREST study showed no significant benefit over everolimus. Further studies are needed to confirm the use of axitinib, as the ATLAS trial showed statistically significant results in DFS in higher-risk population based on investigator assessment, but not based on independent central review. Therapy with 5-FU, α-IFN and IL-2, atezolizumab, sorafenib, thalidomide, nivolumab + ipilimumab should not be used in the adjuvant setting.