Introduction Tuberculosis is an important health problem: it is estimated to be among the leading causes of death and disability among the economically active segment of the world’s population. It primarily impacts low income countries where resources for dealing with health are severely constrained. Even so, tuberculosis control merits priority as an intervention in the health sector, as national tuberculosis programmes are among the most cost-effective of any health intervention in low income countries. Objectives To identify the factors responsible for non-compliance among tuberculosis patients in Kailali district Nepal. Methods A cross-sectional study was conducted between December 2004 to March 2005, among 130 compliant and 25 non-compliant tuberculosis patients, randomly selected four DOTS treatment centres, using a structured questionnaire with face to face interview. Patients were deemed to be non-compliant when they had missed more than 7 consecutive days of treatment. Results About half (48%) of non-compliant were more likely to think that treatment could be stopped once they were free of symptoms and thought they were cured. Adherence proportion was high among the higher education group (p<0.05). The overall knowledge scores (p<0.001) were statistically significant difference between the compliant and non-compliant patients. A significant relationship was found between compliance behavior and availability of health workers at DOTS centre (p<0.05), DOT (p<0.001), mode of transportation, and traveling time (p<0.001). Conclusion Compliance is affected by educational level, knowledge, availability of health workers, DOT, and traveling time. It could be improved by provision of more information about tuberculosis and expansion of DOTS near to the patient’s home.