To evaluate the efficacy of a mindfulness-based treatment (MBT) for smoking cessation or reduction and compare it with that of cognitive behavioral therapy (CBT). This was a single-center randomized controlled clinical trial including 113 patients divided into two groups: MBT (n = 54) and CBT (n = 59). The interventions comprised eight 90-min sessions. The primary outcome was smoking cessation at 16 weeks after program initiation. Secondary outcomes included reduction in the mean number of cigarettes smoked/day at 16 weeks after treatment initiation, as well as smoking cessation and reduction in the number of cigarettes smoked/day at the last program session. Participants had to attend ≥ 50% of the sessions to be included in the primary outcome analysis. An intention-to-treat analysis was also performed. There was no difference between the groups regarding the primary outcome (30.4% in the MBT group vs. 31.6% in the CBT group, p = 0.68) or immediate abstinence rates (47.8% in the MBT group vs. 36.8% in the CBT group, p = 0.47). Both treatments were equally effective in reducing the number of cigarettes smoked/day at the last program session (a reduction of 93.33% [0-100%] in the MBT group and of 70% [33.3-100%] in the CBT group, p = 0.92) and at 16 weeks after program initiation (a reduction of 57.1% [0-100%] in the MBT group and of 70% [25-100%] in the CBT group, p = 0.49). MBT appears to be as effective as CBT for smoking cessation or reduction and can be an option for the treatment of tobacco use disorders in Brazil (Brazilian Registry of Clinical Trials identifier: RBR-3w2scz [http://www.ensaiosclinicos.gov.br]).