OBJECTIVES: To compare the costs and outcomes of therapy with itraconazole solution (IS) versus alternative therapies in treating oral candidiasis (OC) in HIV/AIDS patients in the U.S. and Canada. METHODS: Three clinical decision-analytic models were developed for each country to evaluate the cost-effectiveness of treating mild, moderate, and severe OC in HIV/AIDS patients. Data for the models were derived from published studies and a survey of American and Canadian clinical experts. Outcomes included adverse events, lack of response to therapy, relapse, and cure. RESULTS: First line treatments of mild OC in Canada were nystatin suspension or nystatin suppository. Fluconazole replaced nystatin suspension in treating moderate OC. Mild and moderate OC were treated with fluconazole and clotrimazole in the U.S. First line treatments for severe OC were fluconazole and ketoconazole in both countries. The expected cost of treating each severity level of OC was lower in Canada. In both countries, therapy with IS yielded greater costs and cure rates than clotrimazole or nystatin, respectively, resulting in cost-effectiveness values for IS of $125 to $1891 (all costs in 1998 U.S. dollars). IS was dominant over fluconazole in Canada, and had a cost-effectiveness ratio relative to fluconazole of $300 to $364 in the U.S. Sensitivity analyses indicate the above results were robust with respect to changes in model parameters. CONCLUSIONS: Alternative therapies in both countries for OC were different but model results were similar. Treatment with IS led to greater cure rates in all scenarios, was cost-effective in the U.S., and was cost-effective or cost-saving in Canada. As such, IS is likely an appropriate choice for treating OC in this population.