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Introduction The self-medication hypothesis suggests that patients diagnosed with schizophrenia might smoke as an attempt to self-medicate theirsymptoms. As a consequence, smoking cessation could worsen their clinical status. Objectives To assess the clinical changes associated with tobacco cessation in a sample of smoking outpatients with schizophrenia. Methods Sample: 63 smoking outpatients with DSM-IV Schizophrenia from three Mental Health Centers located in Northern Spain [77.0% males; mean age (SD) = 43.90 (8.72); average daily cigarette use (SD) = 27.99 (12.55)]. Instruments: (1) Clinical symptoms: Positive and Negative Symptoms Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI). (2) Pattern of tobacco use: n° cigarettes/day; Expired carbon monoxide (CO ppm). Design: A quasi-experimental design with two groups was implemented: control group (GC − 18 patients not willing to stop smoking), and treatment group [TG − 45 patients in smoking cessation supported by nicotine patches or vareniclina (12 weeks)]. Patients were evaluated at baseline and at week 11 (end of program). Paired sample t-test was used to detect changes in clinical symptoms from baseline to follow-up. Results 23.1% stopped smoking (from TG). No significant differences were found between baseline and follow-up scores (p>.05) among smokers and abstinent in PANSS subscales, HDRS and CGI. Conclusions Tobacco cessation did not have a significant effect on the clinical symptoms of this group of patients. Further studies should analyze the stability of these outcomes at longer follow-ups to confirm our results. [ABSTRACT FROM AUTHOR]