OBJECTIVE: To perform a systematic review of interventions used to reduce adverse events in surgery. BACKGROUND: Many interventions, which aim to improve patient safety in surgery, have been introduced to hospitals. Little is known about which methods provide a measurable decrease in morbidity and mortality. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception to Week 19, 2012, for systematic reviews, randomized controlled trials (RCTs), and cross-sectional and cohort studies, which reported an intervention aimed toward reducing the incidence of adverse events in surgical patients. The quality of observational studies was measured using the Newcastle-Ottawa Scale. RCTs were assessed using the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Ninety-one studies met inclusion criteria, 26 relating to structural interventions, 66 described modifying process factors. Only 17 (of 42 medium to high quality studies) reported an intervention that produced a significant decrease in morbidity and mortality. Structural interventions were: improving nurse to patient ratios (P = 0.008) and Intensive Care Unit (ITU) physician involvement in postoperative care (P < 0.05). Subspecialization in surgery reduced technical complications (P < 0.01). Effective process interventions were submission of outcome data to national audit (P < 0.05), use of safety checklists (P < 0.05), and adherence to a care pathway (P < 0.05). Certain safety technology significantly reduced harm (P = 0.02), and team training had a positive effect on patient outcome (P = 0.001). CONCLUSIONS: Only a small cohort of medium- to high-quality interventions effectively reduce surgical harm and are feasible to implement. It is important that future research remains focused on demonstrating a measurable reduction in adverse events from patient safety initiatives.