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 <0.0001), but not in cardiac surgery (OR = 0.93 [95% CI 0.70–1.24], p = 0.61) (psubgroup= 0.002). Higher incidence of AKI was present in cardiac surgery patients receiving perioperative statins (RR = 1.15 [95% CI 1.00–1.31], p = 0.05), nonetheless not in non-cardiac surgery (RR = 1.52 [95% CI 0.71–3.26], p = 0.28) (psubgroup= 0.47). No difference in postoperative stroke and mortality was present in either cardiac or non-cardiac surgery. However, low risk of bias trials performed in cardiac surgery showed a higher mortality with statins versus placebo (OR = 3.71 [95% CI 1.03–13.34], p = 0.04). Subgroup and meta-regression analyses failed to find possible relationships between length of statin regimens and clinical outcomes. Trial sequential analysis suggested no firm conclusions on the topic. Conclusions: Perioperative statins appear to be protective against postoperative myocardial infarction in non-cardiac surgery and associated with higher AKI in cardiac surgery. Possible positive or even negative effects on mortality could not be excluded and merits further investigations. Currently, no randomized evidence supports the systematic administration of statins in surgical patients. © 2018, The Author(s).