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The purpose of this article is to compare the efficacy of two prominent medications utilized in smoking cessation: bupropion and varenicline.Comprehensive review of the literature on bupropion and varenicline including randomized control trials, government reports, journal reviews, and pharmaceutical inserts.In all studies comparing varenicline to bupropion and/or placebo, varenicline yielded a greater cessation rate at both 3 and 12 months. Additionally, varenicline 1 mg indicated an increased potential for long-term cessation success when compared with varenicline 0.5 mg. When compared with only placebo, bupropion demonstrated a higher efficacy for cessation both at 3 and 12 months.Only 6% of the 20 million smokers who attempt to quit will succeed in long term. Clinicians must assess their patient's willingness to quit and educate them about cessation options. Knowing the efficacy of various treatment options for patients will potentially increase their success at quitting smoking. Understanding the treatment options available, allows for clinicians to provide the best possible method for smoking cessation for their patient population.