Drug-resistant tuberculosis is a major public health problem. The aim of this study was to assess the local susceptibility patterns of Mycobacterium tuberculosis and clinical outcomes of drug resistant tuberculosis (DR-TB) at Srinagarind Hospital, a tertiary care center in northeastern Thailand. Between January 2004 and December 2008, 1,052 patients had culture-proven M. tuberculosis infections at Srinagarind Hospital. M. tuberculosis was resistant to isoniazid (2.3%), rifampicin (2.8%), ethambutol (3.8%), streptomycin (2.1%), kanamycin (0.7%) and ofloxacin (1.9%). The occurrences of multi-drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) were 1.2% and 0.38%, respectively. Of the 65 DR-TB patients, complete medical records were found for 55. The male to female ratio was 2.2:1. The mean age was 50 years. Thirteen patients had MDR-TB. The duration of symptoms in the MDR-TB group was longer than the non-MDR-TB group, 11.6 months vs 2.6 months, respectively. Half of MDR-TB and one-third of non-MDR-TB patients had a previous history of being treated for tuberculosis. Nearly 20% of cases were HIV positive. Mono-drug resistance was initially treated with standard first-line drugs (CAT 1). The clinical course was more likely to be worse during the maintenance phase if there was resistance to rifampicin. Whenever there was resistance to two, three or four drugs, the antituberculosis drugs were prescribed based on susceptibility patterns. Only 30% of patients with MDR-TB and XDR-TB responded to treatment. Culture and sensitivity testing for M. tuberculosis cases is recommended in patients at high risk for DR-TB, such as patients previously treated for tuberculosis and those HIV positive.