Patients with previous myocardial infarction (MI) have a high risk of recurrence. Little is known about the effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients with a previous MI and left main or multivessel coronary artery disease (CAD). We compared long-term outcomes of these 2 strategies in 672 patients with previous MI and left main or multivessel CAD, who underwent CABG (n = 349) or PCI with DES (n = 323). A pooled database from the BEST, PRECOMBAT, and SYNTAX trials was analyzed, and the primary outcome was a composite of death from any causes, MI, or stroke. Baseline characteristics were similar between the 2 groups. The median follow-up duration was 59.8 months. The rate of the primary outcome was significantly lower with CABG than PCI (hazard ratio [HR] 0.59, 95% CI 0.42 to 0.82; p = 0.002). This difference was driven by a marked reduction in the rate of MI (HR 0.29, 95% CI 0.16 to 0.55, p <0.001). The benefit of CABG over PCI was consistent across all major subgroups. The individual risks of death from any causes or stroke were comparable between the 2 groups. Conversely, the rate of repeat revascularization was significantly lower with CABG than PCI (HR 0.34, 95% CI 0.22 to 0.51, p <0.001). In conclusion, in the patients with previous MI and left main or multivessel CAD, compared to PCI with DES, CABG significantly reduces the risk of death from any causes, MI, or stroke.