BACKGROUND: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. METHODS: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. RESULTS: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0-1 mm) was 0.54 (95% confidence interval = 0.30-0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31-0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11-0.88) among girls and 0.84 (0.39-1.82) among boys; and for BCG scar, the results were 0.41 (0.21-0.82) and 0.88 (0.34-2.30), respectively. CONCLUSIONS: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.