Purpose: To determine whether the combination of bupropion SR and varenicline offers improved smoking cessation outcomes compared to varenicline monotherapy or to combination of bupro-pion SR and nicotine patch. Methods: This retrospective chart review included 489 volunteer enrolees in a Veterans Affairs (VA) tobacco cessation clinic who received one of the three treatments upon clinic enrolment. The study endpoints were smoking cessation and clinic completion rates, changes in the number of cigarettes smoked, carbon monoxide (CO) levels, urges to smoke, self-confidence to quit and medication-attributed adverse effects. Results: The relative smoking cessation rates were 33%, 32%, and 40% for bupropion SR and nicotine patch, bupropion SR and varenicline, and varenicline groups, respectively. The 0.21 p value established that no significant cessation rate differences existed between any of the groups. Varenicline alone or in combination was as well tolerated as the combination of bupropion SR and nicotine patch. Conclusions: The combination of bupropion SR and varenicline did not demonstrate any smoking cessation advantage over varenicline monotherapy or the combination of bupropion SR and nicotine patch and therefore do not support the use of bupro-pion SR and varenicline over varenicline monotherapy.