Abstract Background While coronary artery bypass grafting (CABG) is the standard treatment for patients with multi-vessel coronary artery disease (CAD), percutaneous coronary intervention (PCI) has been an alternative approach. The study aims to evaluate the long-term outcomes of PCI versus CABG in treating patients with CAD. Methods A total of 9569 patients with CAD (age 68.60±12.24 years, 81.7% men) who underwent PCI (n=7429) or CABG (n=1635) were retrospectively recruited from January 2000 to December 2014 at a tertiary medical center. Propensity score-matched analysis were conducted. The primary outcome was all-cause mortality during a 10-year follow-up duration. Results During a median follow-up duration of 6.97±4.54 years, there were 1634 deaths. Crudely, there was no difference in 10-year mortality between PCI and CABG groups (26.3% vs. 23.02%; P= 0.135). After accounting for age, renal function, previous myocardial infarction, and heart failure, the 10-year survival rate remained similar between the two groups. The subgroup analysis showed inferior outcomes with PCI than CABG if any bare-mental stent (BMS) was used (10-year risk of mortality 36.1% vs. 24.7%; P= 0.032). In addition, CABG was also associated with better survival than PCI in diabetic subjects (10-year risk of mortality 24.9% vs. 30.9%, P=0.086). In contrast, PCI demonstrated superior long-term benefits in subjects with left main (LM) and single-vessel disease, whereas CABG showed better long-term outcomes for individuals with left main (LM) and multivessel disease. Conclusions PCI demonstrated comparable long-term outcomes with CABG in treating subjects with CAD when purely drug-eluting stents were used. Any use of BMS is not encouraged to treat patients with left main or multivessel CAD. In contrast, PCI was related to superior long-term survival among patients with LM and single-vessel disease.