A case-control study was conducted in the greater Houston area to determine risk factors for late-onset group B streptococcus (GBS) disease (onset of disease or first positive culture between 7 and 180 days after birth). Characteristics of 122 case patients diagnosed during 1995-2000 were compared with control subjects matched for birth hospital and date of birth. Half the case patients were preterm infants, 84% of whom were born at <34 weeks of gestation. The risk for late-onset GBS disease increased by a factor of 1.34 (95% confidence interval [CI], 1.15-1.56) for each week of decreasing gestation, by 3.70 (95% CI, 1.35-10.1) for infants of black mothers, and by 4.15 (95% CI, 1.27-13.60) for infants of mothers with a positive GBS screening. These risk factors are similar to that of early-onset GBS disease. However, prematurity is the major risk factor for late-onset GBS disease.