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Background We aimed to undertake a systematic review and meta-analysis of studies addressing perioperative natriuretic peptide (NP) levels to predict postoperative major adverse cardiac events (MACE) after major surgery. Methods We searched MEDLINE and Embase with no language restrictions up to May 2013. The end points were major cardiac complications. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. Results Of the 662 retrieved articles, 24 studies satisfied the predefined eligibility criteria, including 5438 patients along with 712 (13.1%) events. After major surgery, the diagnostic odds ratio (DOR) of NP in predicting postoperative MACE was 14.3 (95% confidence interval [CI], 9.87-20.7) for overall population, 13.9 (8.43-22.8) for patients undergoing cardiac surgery, and 15.0 (8.84-25.5) for patients undergoing noncardiac surgery. The pooled sensitivity was 0.84 (95% CI, 0.79-0.88) and specificity was 0.76 (95% CI, 0.71-0.81). Postoperative measurement (DOR, 18.9; 7.68-46.3) was associated with higher predictive value than preoperative measurement (DOR, 13.6; 7.68-46.3). Results were similar for a subgroup with the composite outcome including mortality (DOR, 16.4; 10.6-25.5). B-type natriuretic peptide was associated with higher predictive accuracy (area under the summary receiver operating characteristic, 0.84; 0.81-0.87) than N-terminal pro–b-type natriuretic peptide (area under the summary receiver operating characteristic, 0.90; 0.87-0.92). Conclusions The existing literature suggests that perioperative NP testing have reasonable accuracy and can be useful in perioperative risk stratification. Natriuretic peptide testing has high rule-out value and low rule-in value for predicting postoperative MACE. Medical decisions should be made in the context of these characteristics.