Rationale: Individuals living with patients with tuberculosis (TB) are at elevated risk of infection and disease, with children at greatest risk. The World Health Organization recommends isoniazid preventive therapy (IPT) for HIV-positive contacts and those younger than 5 years. Despite these recommendations, household-level IPT programs are rarely implemented in high TB burden settings. Evidence is scarce about the age-specific efficacy of interventions, such as IPT and bacillus Calmette-Guérin (BCG) vaccination for preventing TB disease among exposed contacts. Objectives: We estimate the age-specific efficacy of IPT and BCG for preventing TB disease using data from a large observational prospective cohort study of household contacts of patients with TB in Lima, Peru. Methods: We identified all adults (> 15 yr) with incident pulmonary TB (index cases) diagnosed at 106 public health centers in Lima from September 2009 to August 2012. Among 14,041 household contacts (of 3,446 index cases) assessed for infection and disease during the yearlong follow-up period, we identified 462 additional TB cases. We estimate risk ratios (RR) for pulmonary TB associated with BCG, IPT, and latent TB infection. Measurements and Main Results: BCG confers protection against coprevalent and incident TB among HIV-negative children younger than 10 years (RR, 0.35; 95% confidence interval, 0.19-0.66). IPT confers protection against incident TB among HIV-negative contacts younger than 30 years (RR, 0.33; 95% confidence interval, 0.20-0.54). Risk of incident TB associated with latent TB infection is greatest for children younger than 5 years and decreases with age. Conclusions: These findings support the use of IPT in older children and young-adult household contacts, in addition to children younger than 5 years. Copyright © 2014 by the American Thoracic Society.