Legal restrictions have contributed to the decline in smoking prevalence in several European countries. We investigated the impact of the Italian 2005 indoor smoking ban on the efficacy of counseling alone or in combination with bupropion for smoking cessation. Before and after the introduction of the ban (2001-2006), 550 smokers were enrolled in the smoking cessation program in Rome and were asked to choose between a 6-week group counseling therapy (GCT) given alone or in combination with 7 weeks of daily bupropion. Follow-up was completed 12, 26, and 52 weeks after the quit day. Due to the observational nature of the study, we used propensity scores to match 138 and 290 subjects (pre-/postban) in the bupropion- and GCT-only groups, respectively. Covariate balance in the two matched samples was adequate for all variables except "coffee consumption" in the GCT-only group. The regression adjusted odds ratios indicated that the introduction of the ban resulted in 52% reduced odds of continued smoking at 12 months among the GCT + bupropion group and 41% reduced odds in the GCT-only group. We observed that the ban was associated with both increased 12-month abstinence rates and motivation to quit. In a mediation analysis, we determined that the total effect of the smoking ban on the abstinence rate was reduced after controlling for motivation, which confirmed that motivation was a partial mediator. The introduction of an indoor smoking ban improved the efficacy of smoking cessation treatments by possibly providing a setting that increased the level of motivation to stop smoking.