This study compares the effectiveness and tolerability of bupropion versus bupropion plus nicotine patch for smoking cessation in a routine clinical setting. Patients at the Sepulveda Veterans Health Administration Smoking Cessation Clinic completed a baseline survey and received counseling over 2 months, along with bupropion or bupropion plus nicotine patch. Of the 227 patients randomized to treatment, 112 (49%) received bupropion only and 115 (51%) received the combination therapy. At least one side effect was noted in 55% of bupropion patients and 70% of combination therapy patients; treatment regimens were changed in 7% and 14%, respectively. Abstinence rates at 2 months were 26% for the bupropion group and 37% for the combination therapy group (p = 0.1), and at 6 months were 42% versus 35%, respectively (p = 0.4). Although 6-month abstinence rates were derived from patient self-report and should be interpreted with caution, these results suggest that most patients referred to the clinic are able to take these medications. There was no difference in the rate of switching treatments, or in long-term abstinence rates.