Objective: Aim of the study is to evaluate factors affecting treatment success among individuals receiving varenicline therapy for smoking cessation. Material and Methods: This research was carried out at Istanbul Medeniyet University Göztepe Training and Research Hospital between January 2018 and January 2019. A total of 209 patients in the smoking cessation outpatient clinic who were treated with varenicline Varenicline were constituted into the study group. The Fagerstrom Nicotine Dependence Level Test (FTND) was used to determine individuals' nicotine addiction levels, and the Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression levels. Results: There were 90 (43.1%) women and 119 (56.9%) men in the study group and mean age was 41.34 ± 10.93 (21-64) years. Overall, 63.2% (n=132) of varenicline recipients quit smoking. The frequency of quitting smoking due to physician advice was higher in those who quit than those who did not (p=0.011). Multiple logistic regression revealed that the independent factors associated with the lower likelihood of smoking cessation were higher number of cigarettes per day (p=0.008), higher HADS-Total score (p<0.001), post-treatment nervousness (p=0.046), and post-treatment depressive mood (p=0.007), whereas being able to remain smoke-free for longer periods in previous quitting attempts was associated with higher likelihood of success (p=0.005). Conclusion: The success of smoking cessation with varenicline therapy is lower in the presence of the following factors: having high risk for anxiety and depression, smoking a greater number of cigarettes per day, shorter periods of remaining smoke-free in previous quitting attempts, and experiencing nervousness during withdrawal. Receiving physician advice to quit also appears to increase the chance of quitting smoking. Keywords: Smoking; Smoking Cessation; Smoking Cessation Agents; Varenicline; Anxiety; Depression