The aim of this work was to assess the efficacy of itraconazole and allopurinol in chronic Chagas disease. Two hundred two subjects (137 infected, 59 with Chagas cardiopathy and 6 with non chagasic cardiopathy) were randomly assigned to be treated with itraconazole (87 subjects receiving 6 mg/kg/day for 120 days), allopurinol (68 subjects receiving 8.5 mg/kg/day for 60 days) or placebo (47 subjects during 60 days). Medications were well tolerated. Indirect hemagglutination test was modified in 5 subjects (3.2%) after treatment. Initially positive xenodiagnosis became negative in 34 of 36 subjects (94.4%) treated with itraconazole and 8 of 10 subjects (80%) treated with allopurinol. Initially normal EKG was not modified in 100% of patients receiving placebo, 84.9% receiving itraconazole and 86.7% receiving allopurinol. Initially abnormal EKG became normal in 10 of 31 subjects (32%) receiving itraconazole, 8 of 20 (40%) receiving allopurinol and none of 8 receiving placebo. It is concluded that xenodiagnosis and EKG improvements indicate that itraconazole and allopurinol have a role in the treatment of chronic Chagas disease. A 36 months follow up of these patients will help to confirm this conclusion.