Isoniazid chemoprophylaxis recommendations include its use in persons who have positive tuberculin reactions, but neither recent conversion nor other activation risk factors, only if they are under age 35 years. Above this threshold, the isoniazid hepatitis risk is said to outweigh the benefit of preventing activation. Because this policy is controversial, we performed a decision analysis contrasting those who take with those who decline isoniazid therapy according to three outcome measures: life expectancy, likelihood of illness (isoniazid hepatitis and active tuberculosis), and likelihood of fatal illness. We found no threshold between ages 10 and 80 years by the measures of life expectancy and likelihood of fatal illness; isoniazid benefits outweigh risks for all, though the margin is small for the elderly. A threshold exists only in the likelihood of illness: isoniazid risks outweigh benefits for those aged 50 to 65 years. Only extreme variations of assumptions affect these findings. Chemoprophylaxis recommendations should include low-risk tuberculin reactors over age 35 years.