Background. Low and deficient levels of Vitamin A are common in low-And middle-income countries where tuberculosis burden is high. We assessed the impact of baseline levels of Vitamin A and carotenoids on tuberculosis disease risk. Methods. We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary tuberculosis case patients in Lima, Peru. We defined case patients as human immunodeficiency virus (HIV)-negative HHCs with blood samples in whom tuberculosis disease developed ≥15 days after enrollment of the index patient. For each case patient, we randomly selected 4 controls from among contacts in whom tuberculosis disease did not develop, matching for sex and year of age. We used conditional logistic regression to estimate odds ratios for incident tuberculosis disease by Vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors. Results. Among 6751 HIV-negative HHCs with baseline blood samples, 192 had secondary tuberculosis disease during follow- up. We analyzed 180 case patients with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline Vitamin A deficiency was associated with a 10-fold increase in risk of tuberculosis disease among HHCs (adjusted odds ratio, 10.53; 95% confidence interval, 3.73-29.70; P < .001). This association was dose dependent, with stepwise increases in tuberculosis disease risk with each decreasing quartile of Vitamin A level. Conclusions. Vitamin A deficiency strongly predicted the risk of incident tuberculosis disease among HHCs of patients with tuberculosis. Vitamin A supplementation among individuals at high risk of tuberculosis may provide an effective means of preventing tuberculosis disease.