While various behavioral and pharmacologic agents have proven to be effective and safe for continued smoking cessation, a combination of varenicline and nicotine replacement (NRT) with transdermal patches has not been shown definitively to be more efficacious than varenicline alone. In the framework of a randomized clinical trial (RCT), the present study evaluates whether a combination of varenicline with NRT improved smoking cessation rates and abstinence duration compared with varenicline alone.