AimsTo compare success rates and characteristics of smokers treated a second time by a smokers' clinic with success rates of their first treatment. DesignRetrospective cohort study. SettingTobacco Dependence Treatment clinic in Prague, Czech Republic, between 2005 and 2017. ParticipantsA total of 5225 smokers treated either once (n = 5006, single treatment sample, SS) or also second time (n = 219, re-treated sample, RS), on average 4.47 years after the first visit. InterventionSmokers received intensive treatment of tobacco dependence with pharmacotherapy options. Outcomes were evaluated after 1 year. In case of failure or relapse, participants could undergo re-treatment in the same setting at least 1 year after the start of the first treatment. MeasurementsTwelve-month self-reported continuous abstinence; CO-validated (<= 6 parts per million); number of visits; type of pharmacotherapy; mental health history; Fagerstrom Test for Cigarette Dependence; time between first and second treatment. ResultsThe abstinence rate in the SS was 34.8% [95% confidence interval (CI) = 33.4%, 36.1%] and in the RS was 37% (95% CI = 30.6%, 43.8%) and 39.7% (95% CI = 33.2%, 45.5%) for their first and second treatments, respectively. The samples were comparable on smoking and socio-demographic characteristics and pharmacotherapy used, but the RS in the second treatment had a higher prevalence of diagnosed mental health disorder at 39.3% (95% CI = 32.8%; 46.1%) compared with 23.7% (95% CI = 22.5%; 24.9%) in the SS. Participants who initiated their second quit attempt 1 to 2 years after the first one were less successful than those who initiated their second quit attempt later (25 versus 43%; P < 0.05). The results of the first treatment cycle were not found to be a reliable predictor for outcomes of the second cycle of treatment in univariate or multivariate logistic regression (odds ratio = 1.35, 95% CI = 0.70-2.63, P = 0.373). ConclusionIn Prague, Czech Republic, smokers re-attending stop-smoking treatment more than 2 years after their previous quit attempt appear to achieve similar success rates to those being treated for the first time.