BackgroundAlthough some studies have shown potential benefit for ischemic postconditioning (IPoC) during primary percutaneous coronary intervention (PCI) in improving surrogate markers of reperfusion and infarction size, the benefit of this approach on clinical outcomes remains unknown.Methods and ResultsElectronic databases were searched for randomized clinical trials that compared IPoC versus conventional treatment during primary PCI. Random effects DerSimonian‐Laird risk ratios (RR) were calculated for different clinical and surrogate outcomes. The main outcome of this analysis was all‐cause mortality. A total of 25 trials involving 3,619 patients were included in the analysis. At a mean follow up of 14 months (95% confidence interval (CI) 8.6–19.4 months), the incidence of all‐cause mortality was 4.9% [95% CI 3.8–6.0%] in the IPoC group versus 3.8% [95% CI 1.9–5.7%] in the control group (RR 0.92, 95% CI 0.68–1.24,P = 0.74). The risk of reinfarction (2.7% [95% CI 1.1–4.3%] vs. 2.3% [0.6–4.0%]; RR 1.29, 95% CI 0.62–2.68,P = 0.72), heart failure (3.6% [95% CI 2.0–5.1%] vs. 5.7% [95% CI 3.3–8.2%]; RR 0.77, 95% CI 0.58–1.06,P = 0.24), target vessel revascularization (3.2% [95% CI 1.7–4.7%] vs. 2.4% [95% CI 1.4–3.3%]; RR 1.40, 95% CI 0.90–2.20,P = 0.20), and stent thrombosis (2.4% [95% CI 1.1–3.8%] vs. 1.8% [95% CI 0.5–3.2%]); RR 1.50, 95% CI 0.60–3.70,P = 0.40) was similar in both groups.ConclusionsIPoC does not appear to reduce the risk of clinical adverse events in patients with ST‐elevation myocardial infarction undergoing primary PCI. © 2017 Wiley Periodicals, Inc.