OBJECTIVES: To explore patient and health worker perspectives on adherence to tuberculosis preventive therapy (TBPT), and to derive lessons for improving access to care amongst human immunodeficiency virus (HIV) infected individuals in resource-poor settings. DESIGN: Both quantitative and qualitative methods were employed. Patient records were reviewed for HIV-positive individuals attending a hospital-based HIV clinic between January 2000 and March 2002. Eighteen patients and two health care workers underwent in-depth interviews exploring perspectives around adherence. RESULTS: Of 229 HIV-positive clinic attendees, 94 (41.0%) were eligible for TBPT. Of 87 patients initiating a 6-month TBPT course of isoniazid 300 mg daily, 41 (47.1%) completed TBPT. Of the 46 interrupters, 16 (34.7%) did not return to the clinic after receiving their first dose of TBPT. Barriers to adherence included fear of stigmatization, lack of money for food and transport, the belief that HIV is incurable, competition between Western and traditional medicine, and a reluctance to take medication in the absence of symptoms. Disclosure of HIV status, social and family support, and a supportive clinic environment positively influenced adherence. CONCLUSION: Interventions to improve the accessibility and quality of the care delivery system have the potential to support adherence to TBPT and other HIV care regimens, including antiretroviral therapy.