In the present study, we characterised drug-resistance patterns, compared treatment outcome between extensively and nonextensively drug-resistant tuberculosis (non-XDR-TB) cases, and assessed risk factors for poor outcome in a high-prevalence country that screens all TB patients for first-line anti-TB drug resistance. We reviewed drug susceptibility test results among all pulmonary TB cases in Latvia diagnosed from 2000-2004, as well as demographic and clinical characteristics, drug-resistance patterns, and treatment outcomes. During the 5-yr period, 1,027 multidrug-resistant tuberculosis (MDR-TB) cases initiated treatment. Among all cases, the proportion that experienced an outcome of cure or completion increased from 66.2 to 70.2% (p = 0.06 for linear trend). Among the 48 (4.7%) XDR-TB cases, 18 (38%) were cured, four (8%) died, three (6%) defaulted, and treatment failed in 23 (48%). In proportional-hazards analysis, characteristics significantly associated with poor outcome included XDR-TB, being retired, presence of bilateral cavitation, and previous MDR-TB treatment history for those aged ≥55 yrs. Overall, treatment success among all MDR-TB cases increased over time. Strategies to prevent transmission of XDR-TB and to further improve treatment outcome are crucial for the future of TB control in Latvia.