Purpose: The impact of smoking habits on periodontal treatment has not been clearly elucidated. This study aimed to specify the effects of cigarette consumption and nicotine addiction on periodontal therapy. Materials and Methods: In this retrospective case-control study, 20 moderate smokers and 20 non-smokers with severe periodontitis were examined after initial diagnosis, and non-surgical active and supportive therapies for 1-6 years (mean follow-up = 3.37 years). Fagerström's test of nicotine dependence (FTND) was evaluated at re-examination. Treatment efficacy was assessed by periodontal pocket probing depth (PPD) changes and number of teeth lost per year (TL). Bayesian multilevel and regression analyses were performed at site, tooth, and patient levels. Results: During the mean follow-up period of > 3 years including active and supportive periodontal therapies, mean PPD, PPD > 3 mm and PPD > 7 mm percentage reductions were 1.03, 1.48 and 2.57 times statistically significantly less pronounced, respectively, in smokers than in non-smokers. Multilevel analysis showed that the variability of PPD > 7 mm reduction was mainly associated with patient-level factors. Smokers presented a higher risk for periodontitis progression. In smokers, periodontal parameter improvement was less pronounced in the maxilla and molars. The mean TL was related to the FTND score, not to cigarette consumption. Regression analysis did not demonstrate other influences of demographic and periodontal treatment characteristics on treatment outcomes, except patient age. Conclusion: Smoking negatively impacted periodontal treatment outcomes at specific tooth sites (deep pockets, maxillary molars) and periodontitis progression, independent of other risk factors. Keywords: nicotine dependence, periodontitis, smoking, treatment outcomes