The smoking rate among Aboriginal people is more than double the rate of the rest of the Canadian population, and smoking is a major source of morbidity and mortality within this population. Tobacco cessation drug therapy use among Aboriginal smokers is very low. We administered a cross-sectional questionnaire to Aboriginal and non-Aboriginal smokers or recent ex-smokers in 12 First Nations communities in two Canadian provinces from September to December 2004. Participants were asked about smoking cessation advice and perceptions of three drug therapy agents. The overall response rate was 82% (407 Aboriginal and 102 non-Aboriginal smokers or ex-smokers). A substantial proportion reported tobacco cessation or reduction in the previous year (Aboriginal 46% vs. non-Aboriginal 32%). Aboriginal participants were less likely to seek physician services (prevalence OR [pOR] = 0.45, 95% CI = 0.27-0.74, p = .001) and less willing to use nicotine patch (pOR = 0.6, 95% CI = 0.38-0.96, p = .03) or bupropion (pOR = 0.50, 95% CI = 0.29-0.84, p = .008). Among First Nations participants, who receive a drug therapy subsidy, lack of awareness of the subsidy were associated with less willingness to use drug therapy; further, the requirement for a physician prescription was perceived as a barrier. Among all participants, utilization of physician services (pOR = 2.2, 95% CI = 1.50-3.20, p<.001) and receiving drug therapy advice from a physician (pOR = 7.7, 95% CI = 4.17-14.3, p<.001) was associated with willingness to use drug therapy. In conclusion, many Aboriginal smokers are interested in and attempt cessation, but underutilization of physician services and low willingness to use drug therapy may explain their lower use of drug therapy. Physicians need to provide advice on drug therapy, and policy makers should eliminate the need for a physician prescription. Future studies can explore cultural attitudes toward cessation drug therapy and physician services.