Abstract Background The effects of perioperative statin therapy on clinical outcome after cardiac or non-cardiac surgery are controversial. We aimed to assess the association between perioperative statin therapy and postoperative outcome. Methods Electronic databases were searched up to May 1, 2018, for randomized controlled trials of perioperative statin therapy versus placebo or no treatment in adult cardiac or non-cardiac surgery. Postoperative outcomes were: myocardial infarction, stroke, acute kidney injury (AKI), and mortality. We calculated risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI) using fixed-effects meta-analyses. We performed meta-regression and subgroup analyses to assess the possible influence of statin therapy regimen on clinical outcomes and trial sequential analysis to evaluate the risk of random errors and futility. Results We included data from 35 RCTs involving 8200 patients. Perioperative statin therapy was associated with lower incidence of postoperative myocardial infarction in non-cardiac surgery (OR = 0.44 [95% CI 0.30–0.64], p