Introduction: Alcohol consumption and tobacco smoking may have synergistic harmful effects when present in combination. This combination is highly prevalent and associated with a multitude of diseases. Brief alcohol intervention (BAI) may be less effective among persons who drink alcohol and smoke tobacco than among persons who drink alcohol and do not smoke. The aim of this study was to find out whether BAI is more effective among adults who do not smoke than among those who smoke. Methods: This study reports secondary outcome analyses of the randomized controlled trial “Testing a proactive expert system intervention to prevent and to quit at-risk alcohol use.” Among municipal office clients, 1,646 who were aged 18–64 and consumed alcohol in the last year participated. Using latent growth curve models, the impact of BAI was compared by incidence rate ratios (IRRs) of self-reported heavy drinking days and the moderating effect of smoking was investigated. Results: There was no significant difference between intervention and control in reducing heavy drinking days in persons who never smoked (IRR 1.01, 95% confidence interval [CI] 0.92–1.10, p = 0.847), formerly smoked (IRR 0.91, CI 0.77–1.07, p = 0.234), currently smoked less than daily (IRR 0.98, CI 0.86–1.12, p = 0.782) and persons who currently smoked daily (IRR 1.09, CI 0.98–1.22, p = 0.125). Conclusion: The effect of BAI did not differ among study participants who currently smoked as among participants who did not. Although not statistically significant, persons who formerly smoked tended to benefit. Persons who currently smoked did not benefit.