OBJECTIVE To examine health care workers' (HCWs') acceptance of and adherence to isoniazid preventive therapy in the setting of a comprehensive tuberculin skin-testing program. METHODS Descriptive case series. METHODS University-affiliated inner-city public hospital in Atlanta, Ga. METHODS A total of 125 HCWs (91 hospital employees and 34 house staff or medical students [the physician group]) who had a positive tuberculin skin test between July 1992 and January 1994 and were offered isoniazid preventive therapy. METHODS Health care workers with a recent tuberculin skin test conversion were required to have a chest x-ray performed and see a physician and were encouraged but not required to undergo preventive therapy. METHODS Acceptance and initiation of preventive therapy with isoniazid by HCWs, completion of at least 6 months of preventive therapy, and differences between the employee and physician groups. RESULTS All 125 HCWs with a recent positive tuberculin skin test had a chest radiograph performed, 123 (98.4%) saw a physician, and 105 (84%) initiated preventive therapy. Sixty-nine (66%) of the 105off HCWs who initiated preventive therapy (55% of the 125 total) completed at least 6 months of isoniazid therapy. More of the physician group than of the employee group completed preventive therapy (25 of 34 [74%] vs 44 of 91 [48%], respectively; P<.01). Of the 36 HCWs who started but did not complete preventive therapy, 12 discontinued therapy because of an adverse drug effect and 24 were nonadherent. CONCLUSIONS Acceptance of tuberculosis preventive therapy by HCWs was high in the setting of a comprehensive tuberculin skin-testing program, and completion of therapy was much higher in the physician group than in previously reported series.