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To determine the level of and reasons associated with adherence to tuberculosis preventive therapy among asymptomatic HIV-infected individuals in northern Thailand.A prospective cohort study with a 9-month follow-up.A total of 412 HIV-infected persons were enrolled in a tuberculosis preventive therapy programme in a hospital. A 9-month isoniazid regimen was prescribed. Adherence was determined by pill count. Participants who missed a scheduled appointment for more than a month were interviewed. Five focus group discussion sessions were held among those who successfully completed the therapy.Of the 412 participants, 69.4% (286) completed the 9-month regimen. The adherence rate, defined as the proportion of those who took more than 80% of pills, was 67.5% (n = 278). Sex, source of participants and history of physical symptoms were associated with adherence. A significant portion of defaults took place at the beginning of the therapy. Out-migration, denial of HIV status, and perceived side effects of isoniazid were frequently cited as reasons for non-adherence. For those adhering participants, the acceptance of personal HIV status, concern about children and family, and a good health provider relationship were important reasons motivating adherence. Several reminder systems were developed by the participants.Although an isoniazid preventive therapy programme was shown to be feasible, further adjustments on the selection of participants, enrolment process, and follow-up system based on these findings are necessary to increase the adherence.