Background: The SYNTAX score affects clinical outcomes in early studies. However, the prognostic value of the SYNTAX Score for long-term outcomes and differences by SYNTAX score risk stratification in long-term prognosis between medical therapy and percutaneous coronary intervention (PCI) in patients with unstable angina pectoris (UAP) are not well known in the era of new generation drug-eluting stents and medication. Methods: In this single-centre retrospective study, a total of 2364 patients with UAP from January 2014 to June 2017 at Beijing Friendship Hospital were enrolled. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), including all-cause death, cardiac death, nonfatal myocardial infarction and stroke at least 2 years after discharge. Results: In this study, 1695 patients had low SYNTAX scores (<= 22), 432 patients had medium SYNTAX scores (23-32), 237 patients had high SYNTAX scores (>= 33), 1018 received medical therapy, and 1346 patients underwent PCI. Longterm MACEs occurred in 95 patients during the 3.38 +/- 0.99-year follow-up. Compared to the medical therapy group, the PCI group showed lower MACEs and cardiac death in patients with high SYNTAX scores (7.4% vs. 16.7%, P = 0.048; 3.7% vs. 14.6%, P = 0.004) but no reduction in patients with low and medium SYNTAX scores. Cox multivariate regression analysis showed that advanced age, diabetes mellitus, left ventricular ejection fraction (LVEF), hs-CRP and high SYNTAX score were independent predictors for MACEs in the medical therapy group (P < 0.05), whereas chronic kidney disease (CKD) and LVEF were predictors of MACEs in the PCI group. Conclusions: Compared to medical therapy, PCI could only significantly reduce long-term MACEs and cardiac death for patients with high SYNTAX scores but not for patients with low and medium SYNTAX scores. A high SYNTAX score could predict long-term MACEs for UAP patients in the medical therapy group but not in the PCI group.