Several clinical trials have shown that complete revascularization (CR) lowers the risks of revascularization and nonfatal myocardial infarction (MI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease compared with infarct-related artery-only revascularization (IRA-OR). However, individual trials have been underpowered for hard outcomes such as cardiovascular (CV) mortality. Therefore, we conducted an updated meta-analysis representing the largest sample size to date inclusive of contemporary studies comparing CR versus IRA-OR. Pooled risk ratios (RRs) were calculated using random effects model. Data from 11 RCTs involving 7,343 patients showed that compared with IRA-OR, CR was associated with lower CV mortality (RR 0.75; 95% confidence interval [CI] 0.57 to 0.99; p = 0.04), MI (RR 0.70; 95% CI 0.53 to 0.93), and recurrent revascularization (RR 0.38; 95% CI 0.27 to 0.54), but similar all-cause mortality (RR 0.85; 95% CI 0.70 to 1.05). In conclusion, in patients with STEMI and multivessel coronary artery disease, compared with IRA-OR, CR was associated with lower risk for CV mortality, MI, and recurrent revascularization, suggesting that CR should be the standard of care for STEMI patients.