Background and objective Relative effectiveness of smoking cessation medications - varenicline, bupropion and nicotine replacement therapy (NRT) - remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters. Methods In a national smoking cessation program in Taiwan (2012-2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity. Results Participants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19-1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24-1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14-1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01-1.65), men (OR = 1.31, CI: 1.18-1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24-1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04-1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch. Conclusions In smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice.