Fungal infections have become an increasing cause of morbidity in patients with acute leukemia undergoing chemotherapy. Oral candidiasis is prone to develop in these patients, and there is also a risk of the development of esophageal Candida infection. Clotrimazole troches have been previously reported to be effective in the treatment of documented oral Candida infection. This report documents a double-blind controlled study in 30 patients with acute leukemia in which the effectiveness of clotrimazole troches in preventing oropharyngeal candidiasis was assessed. Patients were randomly assigned to receive 10 mg troches of clotrimazole or a placebo three times per day. Mucosal scrapings were obtained weekly and examined directly by smear and culture. There were 28 evaluable patients. Of 12 patients with oral Candida infection, 11 were taking placebo and one received clotrimazole (p = 0.0002). Clotrimazole is effective in preventing oropharyngeal candidiasis.