Young patients with coronary artery disease are undergoing percutaneous coronary intervention (PCI) primarily, with a view to deferring coronary artery bypass grafting (CABG). We investigated the validity of this approach, by comparing outcomes in patients ≤50 years undergoing CABG or PCI. One hundred consecutive patients undergoing PCI and 100 undergoing CABG in 2004 were retrospectively studied to allow for 5 and 12 years follow-up. The two groups were compared for the primary endpoints of major adverse cardiac or cerebrovascular event (MACCE). Diabetes, peripheral vascular disease, and left ventricular ejection fraction <50% were higher in the CABG group. At 5 years, rates of myocardial infarction (MI) (9% vs 1%, P = .02), repeat revascularization (31% vs 7%, P < .01), and MACCE (34 vs 12, P < .01) were greater in the PCI vs the CABG group. Similarly, at 12 years, rates of MI (27.4% vs 19.4%, P = .19), repeat revascularization (41.1% vs 20.4%, P < .01), and MACCE (51 vs 40, P = .07) were greater in the PCI group. There were no differences in major outcomes in patients with 1 or 2VD, at 5 or 12 years. Rates of MI, revascularization, and MACCE were higher in patients with 3VD undergoing PCI (n = 21; MI, 47.6%; revascularization, 66.7%; and MACCE, 19 events) vs CABG (n = 78; MI, 19.2%; revascularization, 20.5%; and MACCE, 31 events); P < .01, for all end points. MACCE was lower in young patients undergoing CABG vs PCI at both 5 and 12 years follow-up, primarily as a consequence of patients with 3VD undergoing PCI having more MI and repeat revascularization. CABG should remain the preferred method of revascularization in young patients with 3VD. © 2019 Wiley Periodicals, Inc.