OBJECTIVE: The optimal treatment modality for left main coronary artery (LMCA) disease is still controversial. The aim of this study was to investigate long-term prognostic determinants of percutaneous coronary intervention (PCI) for LMCA disease and the role of coronary artery disease (CAD) severity in this population. METHODS: A total of 60 consecutive patients who underwent LMCA PCI were enrolled in this study. Baseline demographic and clinical variables were recorded, as well as the SYNTAX score (SS), SS II, and residual SS (rSS). The primary endpoints of the study were all-cause death, non procedural myocardial infarction (MI), and stroke. The patients were then divided into 2 groups: patients without a composite endpoint (Group 1) and those with a composite endpoint (Group 2). RESULTS: Of the 60 patients, 15 (25%) were female and the mean age was 59.8±14.7 years. The median follow-up time was 25 months (range: 12-33 months). A primary composite endpoint was observed in 16 patients (26.7%): mortality occurred in 10 patients (16.7%), 4 (6.6%) experienced MI, and stroke was seen in 2 patients (3.3%). Target vessel revascularization was performed in 3 patients (5%). The mean SYNTAX score (Group 1: 19.9±9.8; Group 2: 26.8±12.2; p=0.029), SS II PCI (Group 1: 27.7 [range: 17.7-36.8]; Group 2: 34.2 [range: 27.9-55.2]; p=0.030) and rSS (Group 1: 0 [range: 0-5]; Group 2: 12.5 [range: 3.5-22.5]; p=0.001) were higher in patients with a composite endpoint. Additionally, creatinine (odds ratio [OR]: 13.098; 95% confidence interval [CI]: 1.471-116.620; p=0.021), non-postdilatation (OR: 8.340; 95% CI: 1.230-56.570; p=0.030), and rSS (OR: 1.157; 95% CI: 1.024-1.307; p=0.019) were independent predictors of a primary composite endpoint. CONCLUSION: CAD severity has prognostic value for mortality, MI, and stroke in patients who undergo unprotected LMCA PCI. An increased initial SS and post-procedural rSS were related to adverse cardiovascular outcomes. The rSS was also an independent predictor of major adverse cardiac and cerebrovascular events and mortality.