This study investigated whether tobacco smoking affected outcomes of brief alcohol interventions (BAIs) in at-risk alcohol-drinking general hospital patients. Between 2011 and 2012 among patients aged 18–64 years, 961 patients were allocated to in-person counseling (PE), computer-based BAI containing computer-generated individual feedback letters (CO), and assessment only. PE and CO included contacts at baseline, 1, and 3 months. After 6, 12, 18, and 24 months, self-reported reduction of alcohol use per day was assessed as an outcome. By using latent growth curve models, self-reported smoking status, and number of cigarettes per day were tested as moderators. In PE and CO, alcohol use was reduced independently of smoking status (IRRs ≤ 0.61, ps < 0.005). At month 24, neither smoking status nor number of cigarettes per day moderated the efficacy of PE (IRR = 0.69, ps > 0.05) and CO (IRR = 0.85, ps > 0.05). Up to month 12, among persons smoking ≤ 19 cigarettes per day, the efficacy of CO increased with an increasing number of cigarettes (ps < 0.05). After 24 months, the efficacy of PE and CO that have been shown to reduce drinking did not differ by smoking status or number of cigarettes per day. Findings indicate that efficacy may differ by the number of cigarettes in the short term.