Pharmacotherapy is a critical adjunct to smoking cessation therapy. Little is known about relative preferences for these agents among smokers in primary care settings. In the context of a population-based clinical trial, we identified 750 smokers in primary care practices and independent of their readiness to quit offered them a free treatment course of either bupropion or transdermal nicotine replacement (TNR). Smokers opting for pharmacotherapy completed standardized contraindication screens that were reviewed by the patient's primary care physician. Most participants (67%) requested pharmacotherapy. Use of pharmacotherapy was positively associated with higher nicotine dependence and readiness to quit. Of the smokers requesting pharmacotherapy, 51% requested bupropion and 49% requested TNR. Choice of bupropion was related to no history of heart disease and no previous use of bupropion. Although potential contraindications to treatments were identified for 21.7% of bupropion and 6.6% of TNR recipients, physicians rarely felt that these potential contraindications precluded the use of these agents. When cost is removed as a barrier, a large proportion of rural smokers are eager to use smoking cessation pharmacotherapy, especially agents that they have not tried before. Although some comorbid conditions and concurrent drug therapies were considered contraindications, particularly to bupropion, physicians rarely considered these clinically significant risks enough to deny pharmacotherapy.