BackgroundThere is a great debate about the role of biopsies per protocol in kidney transplant recipients, and the published studies show contradictory results. We aimed to assess the safety and effectiveness of protocol biopsies in kidney transplant recipients in improving short- and long-term outcomes. MethodsWe conducted searches until July of 2023 to identify all randomized clinical trials (RCT). Studies were identified through search strategies for CENTRAL, MEDLINE, EMBASE, and LILACS. Titles and abstracts were screened independently by 2 authors; 2 authors independently assessed retrieved abstracts and the full text. Assessment of risk of bias was carried out using the Cochrane risk of bias tool. The outcomes of interest were: Acute rejection, graft loss, mortality, glomerular filtration rate, and safety outcomes. Meta-analysis was performed for variables of interest when appropriate. Quality of evidence was assessed using GRADE methodology. ResultsWe screened 5,695 records. Four trials met all eligibility criteria. No benefit of protocol biopsy was found in detecting acute rejection (3 studies RR: 2.0, 95% CI: 0.68–5.85, p = .2) or preventing graft loss at 12 months (2 studies, RR 0.33, 95% CI 0.06–1.72, p = .19). No differences were found between the groups in the glomerular filtration rate at 6 months post-transplantation (2 studies, MD 2.97, 95% CI 1.4–7.3, p = .18). A total of 23 safety events were present in the biopsy group compared to six in the control group. ConclusionNo benefit was found in performing protocol biopsy following kidney transplantation.