Objective: To evaluate the prescribing rate of each type of smoking cessation medication and to identify predictors of a successful cessation outcome among adult smokers newly prescribed each type of smoking cessation medication. Methods: A retrospective cohort study was conducted using general electric health-care clinical data. Andersen’s health service utilization model was used as conceptual framework. An index date was assigned as the 1st day of being prescribed smoking cessation medication. A successful outcome was defined as smokers being successfully abstinent. All the smokers in the cohort were followed up to 6 months after the index date. Smoking status of the cohort was measured at 6-month after the index date. The independent variables were categorized into predisposing, enabling, and need characteristics. Three multivariate logistic regression models were conducted to identify the predictors of successful outcome among adult smokers prescribed each type of smoking cessation medication. All statistical analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA) statistical package at a priori significant level of 0.05. Results: For the year of 2011, there were 886,604 current adult smokers. Among these smokers, varenicline was the most commonly prescribed (n = 32,688, 3.69%), followed by nicotine replacement therapy (NRT) (n = 17,716, 2.00%) and bupropion (n = 1,630, 0.18%). In total, we identified 132,885 adult smokers who were newly prescribed varenicline, 4045 adult smokers newly prescribed bupropion, and 38,001 adult smokers newly prescribed nicotine NRT between 2006 and 2011. Among smokers who were newly prescribed varenicline, male smokers were less likely to be abstinent compared with female smokers (odds ratios [ORs]: 0.88, 95% confidence interval [CI]: 0.85-0.91). Among smokers using bupropion, smokers with depression (OR: 1.55, 95% CI: 1.11-2.16) were more likely to quit compared to those without depression. Conclusions: Findings of this real world study indicate that in 2011, varenicline was the most commonly prescribed smoking cessation medication followed by NRT than bupropion. The different types of cessation medication may be particularly beneficial to certain sub-populations in the real world.