We analyzed whether smoking was associated with major adverse cardiovascular events (MACE) and the progression of coronary atherosclerosis as assessed by coronary computed tomography angiography (CCTA) as screening for coronary artery disease (CAD). We enrolled 443 patients who had all undergone CCTA and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. We divided the patients into smoking (past and current smoker) and non-smoking groups and into males and females, and evaluated the presence of CAD, severity of coronary atherosclerosis and MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization) with a follow-up of up to 5 years. %CAD and the severity of coronary atherosclerosis in the smoking group were significantly higher than those in the non-smoking group. %MACE in males and smokers were significantly higher than those in females and non-smokers, respectively. Interestingly, Kaplan–Meier curves also showed that female non-smokers enjoyed significantly greater freedom from MACE than female smokers (p = 0.007), whereas there was no significant difference in freedom from MACE between male non-smokers and male smokers (p = 0.984). Although there were no significant predictors of MACE in all patients according to a multiple logistic regression analysis, smoking was useful for predicting MACE in females, but not males. In conclusion, smoking was significantly associated with MACE in females, but not males, who underwent CCTA as screening for CAD.