Abstract： Background: Patients with premature triple?vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long?term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long?term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients. Methods: One thousand seven hundred and ninety?two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all?cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization. Results: PCI, CABG, and MT alone were performed in 933 (52.1％), 459 (25.6％), and 400 (22.3％) patients. Both PCI and CABG were associated with lower all?cause death (4.6％ vs. 4.1％ vs. 15.5％, respectively, P < 0.01) and cardiac death (2.8％ vs. 2.0％ vs. 9.8％, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all?cause death and cardiac death versus MT alone (all?cause death: hazard ratio [HR]: 0.35, 95％ confidence interval [CI]: 0.23–0.53, P < 0.01 and HR: 0.35, 95％ CI: 0.18–0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95％ CI: 0.19–0.54, P < 0.01 and HR: 0.36, 95％CI: 0.14–0.93, P = 0.03, respectively). Conclusions: PCI and CABG provided equal long?term benefits for all?cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long?term clinical outcomes.