Both depression and smoking are highly prevalent and related to poorer outcomes in cardiac patients. In this study, the authors examined the association between depressive symptoms and smoking status, described the frequency and type of antidepressant use, and prospectively tested the effects of antidepressant use in smokers on smoking status and psychosocial outcomes. Participants comprised 1,498 coronary artery disease (CAD) outpatients who completed a baseline survey which assessed depressive symptoms, current medications, and smoking status. A second survey was mailed 9 months later that assessed depressive symptoms, anxiety, insomnia and smoking status. Results showed that current and former-smokers had significantly greater depressive symptoms than non-smokers. Ten percent of patients were taking antidepressants, most frequently SSRIs, with significantly more smokers on antidepressants than former and non-smokers. At follow-up, smokers on antidepressants were less likely to have quit, had greater anxiety, depressive symptoms and insomnia than smokers not using antidepressants. This study demonstrated that smokers and quitters with CAD had greater depressive symptoms and use of antidepressants than non-smokers, but that the antidepressants utilized may not be optimizing outcomes.