Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a Chinese population. We enrolled 248 smokers in a hospital-based, randomized, smoking cessation trial conducted at four outpatient centers in Beijing. A total of 123 participants received an 8-week course of sustained-release bupropion (Bup-SR) and 125 participants received 8 weeks of placebo. All participants received brief education and counseling on smoking cessation. We determined rates of abstinence and smoking reduction based on chemical verification and self-report at 8 and 12 weeks. At the end of the medication treatment (8 weeks) and at the end of the trial (12 weeks), the abstinence rates for Bup-SR were 29.3% and 39.8%, respectively, and 10.4% and 8.0% for placebo, respectively (both p < .001). Bup-SR was also superior to placebo in reducing cigarettes per day and urinary cotinine levels. Bup-SR is efficacious for smoking cessation in healthy Chinese patients treated in the outpatient setting. It is well tolerated with a few mild side effects.