Tuberculosis and HIV/AIDS are both prevalent in Southeast Asia and Thailand. Factors related to treatment outcomes in smear-positive pulmonary tuberculosis were evaluated in 226 adult Thai patients. Of these, 31% had a cure or a completion of therapy, 7% had treatment failure or death, and 31% had treatment interruption. The prevalence of co-morbid diseases was 52%, including 19% with HIV. Sputum cultures for Mycobacteria were carried out in 86 cases (38%), 36 of these (42%) were culture positive for Mycobacterium tuberculosis. The rate of drug resistance was 14% (5/36) of culture proven tuberculosis and the mortality rate was 4.6% (7/153) of patients with known outcomes. Of the 7 fatalities, 3 were HIV positive and 1 had multi-drug resistant tuberculosis. Factors that were significantly associated with treatment failure/death were old age (OR 44.1; 95% Cl 2.0-983.7), HIV co-infection (OR 27.5; 95% Cl 1.3-560.0), and previously treated tuberculosis (OR 9.7; 95% Cl 1.6-59.1). These high rates of drug resistance and treatment failure in this area suggest that initial sputum cultures and drug susceptibility testing for Mycobacteria should be performed in all patients who have been previously exposed to anti-tuberculous drugs, and HIV testing should be performed on all patients with tuberculosis.