OBJECTIVE: To identify factors related to dropping out from tuberculosis treatment in health centers in the departments of Managua and Matagalpa, in Nicaragua. METHODS: This study matched cases and controls (1:1 ratio) by age and by municipality of treatment. The 251 cases were patients over 15 years of age who had dropped out of tuberculosis treatment, and the 251 controls were patients who had completed pharmacotherapy, during the period of January 1998 to December 2001. Data were obtained on demographic and socioeconomic characteristics, lifestyle habits, and treatment characteristics. The variables were chosen and grouped using a hierarchical theoretical model. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The risk factors for dropping out of tuberculosis drug treatment were: male gender (OR, 2.51; 95% CI, 1.63 to 3.94), an unstable living situation or being homeless (OR, 3.08; 95% CI, 1.57 to 6.49), changing residence during the treatment period (OR, 4.22; 95% CI, 2.06 to 9.93), consuming alcoholic beverages (OR, 5.25; 95% CI, 2.43 to 12.94), using illegal drugs (OR, 5.25; 95% CI, 2.43 to 12.94), difficulty in access to the health services (OR, 2.64; 95% CI, 1.39 to 5.29), and a negative opinion of the health care received (OR, 5.33; 95% CI, 1.52 to 28.56). CONCLUSIONS: It is essential for the health services in Nicaragua to develop measures to reduce the risk of dropout from treatment. In particular, it is important for the health sector to work with community groups that can support the health sector's activities.