Objective: To evaluate the impact of smoking status on the long-term prognosis of male patients with left main coronary artery lesions who received percutaneous coronary intervention. Methods: A retrospective analysis was conducted. A total of 3122 male patients with left main lesions who received percutaneous coronary intervention in our hospital were categorized by smoking status at admission: 1207 in the non-smokers group, 1339 in the current smokers group, and 576 in the ex-smokers group. The patients were followed up for 3 years. The main study endpoints were major cardiovascular adverse events (composite endpoints of all-cause death, all myocardial infarctions and revascularization) and target lesion failure (composite endpoints of cardiogenic death, target vessel-related myocardial infarction, target vessel-related blood flow reconstruction). Results: The patients in the current smokers group was younger than the non-smokers group and the ex-smokers group (p<0.0001). In terms of prognosis, no statistical significance observed in the incidence of composite end point of MACE (p=0.9866), target lesion failure (p=0.2522), and stent thrombosis (p=0.2118), all-cause death (p=0.3130), cardiogenic death (p=0.2509), revascularization (p=0.5028), target vessel-related revascularization (p=0.9866), and stroke (p=0.3895), among the three groups. The current smokers group had the lowest incidence of myocardial infarction while ex-smokers group had the highest incidence rate(5.67%vs.5.10%vs.2.97%,p=0.0072), and so is the incidence of myocardial infarction related to target vessels (5.48%vs.5.10%vs.2.89%,p=0.0067). According to Cox regression analysis, history of myocardial infarction(HR=1.339，95%CI：1.042-1.722，p=0.0227), and baseline SYNTAX score(HR=1.0333, 95%CI:1.017-1.049,p<0.0001) are independent risk factors of MACE, while current smoking(HR=0.793,95%CI：0.646-0.974,p=0.0274) proves to be an independent protective factor of target vessel related myocardial infarction. Conclusion: For male patients with the left main coronary artery lesions receiving PCI, smoking has no impact on the long-term MACE or target lesion failure, current smoking is an independent protective factor for target vessel related myocardial infarction.