Objective To investigate the prognostic value of SYNTAX score and EURO score in the patients with left main and/or 3-vessel lesions, who received percutaneous coronary intervention (PCI) and conservative treatment because they were not indicated for coronary artery bypass grafting, thus providing clinical guide for individual treatment strategy. Methods Risk scoring systems (EURO score and SYNTAX score) were used for patients with left main and/or 3-vessel lesions confirmed by coronary artery angiography. A total of 115 patients with SYNTAX score> 27 and EURO score> 6 were randomly divided into PCI group and drug group with a follow-up of 18 months. The primary endpoint was the incidence of major adverse cardiovascular events (MACE), consisting of all-cause mortality, non-fatal myocardial infarction, and clinically driven target revascularization. The secondary endpoints included cardioversion, cardiac dysfunction and recurrent angina. Kaplan-Meier method was used for the measurement of survival rate, Log-rank test for survival time distribution, and Cox proportional hazards model for univariate and multivariate analysis. Results In the 18-month follow-up, 6 patients (11.76%) suffered MACEs in the PCI group against 17 patients (34.00%) in the drug group, with a significant higher proportion of non-MACEs in the former than in the latter. Survival curves obtained with the log-rank test in patients without adverse cardiovascular events after discharge showed a significant difference between the two groups (χ²=11.131, P=0.001). The average survival in the PCI group was 12.7 months, and 9.7 months in the drug group. The likelihood ratio test in Cox model showed that the treatment method had an impact on the MACE-free survival time (P=0.001, regression coefficient B=0.882,RR=2.416). Conclusion Mid-term follow-up showed that PCI was better than drug therapy for patients with left main and/or 3-vessel lesions, who were not indicated for coronary artery bypass grafting with a SYNTAX score>27.