OBJECTIVE: We examined factors associated with in-hospital death among children with tuberculosis (TB). We hypothesized that a negative response to tuberculin skin testing (TST) would predict decreased survival. METHODS: This retrospective cohort comprised 2392 children ages 0 to 14 years hospitalized with TB at a Peruvian referral hospital over the 25-year study period. Detailed chart abstraction captured clinical history including TB contacts, physical examination findings, diagnostic data, treatment regimen, and hospitalization outcome. We used Cox proportional hazards regression analyses to determine risk factors for mortality. RESULTS: Of 2392 children, 2 (0.1%) were known to be HIV-positive, 5 (0.2%) had documented multidrug-resistant TB, and 266 (11%) died. The median time from hospitalization to death was 16 days (interquartile range: 4-44 days). Reaction of <5 mm induration on TST predicted death in a multivariable analysis (hazard ratio [HR]: 3.01; 95% confidence interval [CI]: 2.15-4.21; P < .0001). Younger age, period of admission, alteration of mental status (HR: 3.25; 95% CI: 2.48-4.27; P < .0001), respiratory distress (HR: 1.40; 95% CI: 1.07-1.83; P = .01), peripheral edema (HR: 1.97; 95% CI: 1.42-2.73; P < .0001), and hemoptysis (HR: 0.57; 95% CI: 0.32-1.00; P = .05) were associated with mortality. Treatment regimens that contained rifampicin (HR: 0.47; 95% CI: 0.33-0.68; P < .0001) were associated with improved survival. CONCLUSIONS: Negative reaction to TST is highly predictive of death among children with active TB. In children with clinical and radiographic findings suggestive of TB, a negative TST should not preclude or delay anti-TB therapy. Copyright © 2012 by the American Academy of Pediatrics.