AIMS: To compare the efficacy and safety of a novel psychological intervention for smoking cessation called psychodynamic model (PDM) training to an active control condition of sustained-release bupropion. DESIGN: Randomized controlled clinical trial with allocation concealment. SETTING: Private psychiatric practice. PARTICIPANTS: Seven hundred and seventy-nine adult smokers recruited by advertising. INTERVENTIONS: PDM training (n = 366 participants) consisted of a very brief (1.5 days) psychoeducation and a supervised training in autosuggestion techniques (guided imageries) aimed at enhancing self-management, decidedness, assertiveness, security and competence in relationships, natural functions of organs and awareness of bodily functions. Bupropion SR (n = 413) was increased to 150 mg twice daily over 1 week and given over a 8-week period. MEASUREMENTS: Twelve-month continuous abstinence confirmed by exhaled carbon monoxide (CO) of 9 parts per million (p.p.m.) or less at all interviews conducted at 3, 6 and 12 months. FINDINGS: Intention-to-treat analysis revealed Russell standard 12-month continuous abstinence rates of 39.1% in the psychotherapy group versus 12.3% in the bupropion SR group (P < 0.001) with a relative benefit (RB) of 3.16 (2.38-4.26). Completer analysis revealed 12-month continuous abstinence rates of 39.9% in the psychotherapy group versus 22.5% in the bupropion group [P < 0.001; RB 1.78 (1.35-2.34)]. Of note, bupropion abstinence rates were comparable to previous medications/placebo-only comparisons in geographically different samples. CONCLUSIONS: The 1.5-day psychotherapy exceeded bupropion's efficacy, presenting an alternative to pharmacological smoking cessation aids, especially for smokers who reject drugs to treat their substance dependence, at a similar cost (Euro 350) as the bupropion treatment (Euro 355).