Background: Despite the majority of studies have identified smoking as a risk factor for coronary artery calcification (CAC), some studies have not identified this relationship. Differences on results reached by studies on the association of alcohol consumption with CAC exist. Moreover, studies have almost exclusively investigated the association between smoking and alcohol consumption independently. Whether an interaction effect of alcohol on the association of smoking and CAC exists has hardly been investigated. Methods: The data of 2431 adult patients who visited Fuwai Hospital, Chinese Academy of Medical Sciences from September, 2001 to December, 2023 and had Agaston coronary artery calcification score (CACS) reported were utilized. Patients who (1) underwent percutaneous coronary intervention, coronary bypass graft and heart transplantation, or (2) were complicated by acute medical conditions, chronic kidney disease or malignant neoplasms were excluded. Data from 1528 patients were eventually analyzed. Logistic regression was employed to investigate the association of smoking and alcohol consumption with presence of CAC and severe CAC. Interaction effects of alcohol consumption history on the association of current smoking and both presence of and severe CAC were examined. Results: Smoking history was significantly associated with presence of CAC and severe CAC. Current alcohol consumption was also significantly associated with presence of CAC and severe CAC. After adjusting for confounders, alcohol consumption history demonstrated an interaction effect on the association of current smoking with both presence of and severe CAC. Using non-alcohol consumers not smoking at the time of the study as reference, current smokers with an alcohol consumption history suffered from an increased risk of presence of CAC and severe CAC. Conclusions: Both smoking history and current alcohol consumption were associated with presence of and severe CAC. Alcohol consumption history demonstrated an interaction effect on the association of current smoking with both presence of and severe CAC.