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This study aimed to evaluate the effects of psychological intervention and psychological plus drug intervention on smoking cessation among male smokers with single chronic diseases.A total of 509 male smokers were divided into psychological group (n = 290) and psychological plus drugs (n = 219) groups according to their will. The physicians provided free individual counseling and follow-up interviews with brief counseling for all the subjects. In addition to mental intervention, patients in psychological plus drug group also received bupropion hydrochloride or varenicline tartrate to quit smoking. Outcomes were self-reported, regarding the 7-day point prevalence on abstinence rate and continuous abstinence rates at 1-, 3-, and 6-month follow-up period. Data analyses were performed using intention-to-treat analysis and per protocol analysis.With regards to the 3 follow-up time points, 7-day point-prevalence abstinence rate in psychological plus drugs group was all higher than that in the psychological intervention group. Additionally, the 3-month continuous abstinence rate (21.4%) of the 6-month follow-up in the psychological group was not significantly higher than that (26.9%) in the psychological plus drugs group (P >.05 for all). Fagerström test score, stage of quitting smoking, perceived confidence or difficulty in quitting, and chronic disease types were independently correlated with 3-month continuous abstinence in the 6-month follow up (P <.05 for all). The results were similar between intentional analysis and protocol analysis.The psychological intervention and psychological plus drugs intervention exerted good effects on smoking cessation in a short time (1 month). Nevertheless, the advantages did not appear during long-time (6 months) follow-up.