Abstract Body (Do not enter title and authors here): Cigarette smoking is a significant risk factor for coronary artery disease (CAD). However, evidence regarding on the long-term clinical effects of smoking in the Asian population with chronic total coronary occlusion (CTO) is insufficient. This study aimed to assess the effects of smoking on 5-year (median follow-up period 4.2 ± 1.5 years, interquartile range 4.06-5.0 years) clinical outcomes in patients with CTO lesions who had undergone percutaneous coronary intervention (PCI) or medical treatment (MT). We enrolled 681 consecutive patients with CTO who had undergone diagnostic coronary angiography and subsequent PCI or MT. Patients were categorized into smokers (n = 304) and non-smokers (n = 377). The primary endpoint encompassed major adverse cardiovascular events (MACE), including a composite of all-cause death, myocardial infarction (MI), and revascularization over a 5-year period. Propensity score matching (PSM) analysis was used to adjust for potential baseline confounders. After PSM analysis, two propensity-matched groups (200 pairs, n = 400) were generated, and the baseline characteristics of both groups were balanced. The smokers exhibited a higher cardiovascular risk of MACE (29.5% vs. 18.5%, p= 0.010) and non-target vessel revascularization (17.5 vs. 10.5%, p = 0.044) than those of the non-smokers(Table 1). In a landmark analysis using Kaplan-Meier (KM) curvesat the 1-year, the smokers had significantly higher rate of MACE in early period (up to 1-year) (18.8% and 9.2%, p=0.008) compared with non-smokers(Figure 1). Cox hazard regression analysis by propensity score-adjustedwith , revealed that smoking was independently associated with an increased risk of MACE. The findings indicate that smoking is a strong cardiovascular risk factor in patients with CTO, regardless of treatment strategies (PCI or MT) (Figure 2). In addition, in a subgroup analysis, the risk of MACE was most prominently elevated in the group of smokers who underwent PCI.