Introduction. Prophylaxis against tuberculosis has been recognized as important for preventing clinical forms of tuberculosis, mainly in HIV positive patients. However, in countries with high tuberculosis prevalence, prophylaxis application and effectiveness remains controversial.Objective. Effectiveness was established for two prophylaxis regimens -isoniazid treatment for nine months and pirazinamid/rifampin for 60 days.Materials and methods. Two cohort groups of patients diagnosed with HIV/AIDS were compared. One consisted of 131 volunteer patients, who received one of the two prophylactic regimens - pirazinamid/rifampin or isoniazid. The tuberculosis treatment drugs were self-administered andindependent of tuberculin response tests. The second group consisted of 200 patients selected from the records of a HIV/AIDS control program. Follow up for both groups was conducted over a two-year period through clinical records.Results. The 2 groups were similar with respect to clinical and demographic variables. A higher proportion of patients in the control group had CD4 counts <200/ml and viral load>100,000 copies. In the prophylactic group, 8% of patients reported adverse effects due to the drug, and one person had tuberculosis in that group (0.8%). Ten persons in the control group contracted tuberculosis (5%) [RR=0.15, 95%CI 0.02-1.18, p=0.07]. The prophylaxis protective level was calculated to be 80%, after taking into account CD4, viral load, and effective antiretroviral therapy.Conclusion. The prophylaxis against tuberculosis was effective in HIV positive patients, independently of the immune status, viral load, and highly effective antiretroviral therapy.