In patients presenting with ST-segment-elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post-myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment-elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non-ST-segment-elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials. We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45-1.03); P=0.07; multivessel disease following ST-segment-elevation myocardial infarction (RR, 0.84 [95% CI, 0.69-1.04]; P=0.11); non-ST-segment-elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72-0.97]; P=0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75-0.93]; P=0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53-0.90]; P=0.007) and MI (RR, 0.74 [95% CI, 0.62-0.90]; P=0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87-1.11]), cardiac death (RR, 0.89 [95% CI, 0.71-1.12]; P=0.33), or MI (RR, 0.96 [95% CI, 0.86-1.08]; P=0.54). PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.