Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking and received behavioral counseling. Continuous smoking abstinence during weeks 4-7 was the primary endpoint, and long-term smoking abstinence was among the secondary endpoints. Of the original participants, 212 completed the 6-month trial. Continuous smoking abstinence at week 7 was achieved by 43% in the bupropion group and 18% in the placebo group, p<.001. After 26 weeks, 18% and 7%, respectively, were continuously abstinent, p=.008. Side-effects were frequent but simple and reversible in both groups, and generally consistent with the findings of previous studies. Dizziness, insomnia, and pruritus appeared more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark.