Abstract The present study is aimed to assess the safety and efficacy of steroid withdrawal or avoidance (SWA) in high-risk kidney transplant (HRKT). We performed a systematic review of the literature and pooled analysis of the available data concerning SWA following HRKT. HRKT is associated with patients undergoing repeat kidney transplantation, in African American recipients, or in patients with panel-reactive antibody levels >20%. Seven cohort studies and one randomized controlled trial, involving a total of 22 075 patients, were included. Pooled analysis to estimate the risk ratio (RR) and 95% confidence interval (CI) demonstrated comparable graft loss (RR = 0.91, 95% CI 0.76-1.09) between the SWA and corticosteroid maintenance groups, but with reduced mortality in the SWA group (RR = 0.90, 95% CI 0.84-0.98). A subanalysis suggested that SWA was not associated with increased graft loss in patients undergoing steroid withdrawal within 1 week of transplantation, in African American recipients, or in patients with follow-up >5 years. Additionally, SWA was associated with reduced death in those undergoing withdrawal within 1 week (RR = 0.90, 95% CI 0.84-0.98), in African Americans (RR = 0.90, 95% CI 0.83-0.98), and in those with follow-up extended to >5 years (RR = 0.91, 95% CI 0.84-0.98). SWA was not associated with an increased risk of acute rejection (RR = 0.95, 95% CI 0.75-1.21) or cytomegalovirus infection (RR = 1.86, 95% CI 1-3.47); however, it was associated with a reduced risk of posttransplant diabetes mellitus (RR = 0.60, 95% CI 0.37-0.97). SWA following HRKT is safe in terms of graft survival and rejection, and patients undergoing an SWA regimen had a lower risk of death and posttransplant diabetes mellitus. Future prospective studies are required to confirm these findings.