Helicobacter pylori is transmitted within households and high concordance is observed among siblings. To better understand the contributions of close interpersonal contact and family relatedness to transmission, we compared concordance of H. pylori infection among 241 sibling and non-sibling children aged 2-18 years in 68, predominantly low-income, Hispanic households with at least two nuclear families. Prevalence of H. pylori infection was 24%. Compared to children with no infected siblings or non-siblings and adjusting for age, odds of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4 (95% CI 3.1-28.5) for children residing with at least one infected non-sibling, one infected sibling, and with at least one infected sibling and non-sibling, respectively. The study further implicates intersibling transmission as a pathway for H. pylori infection in childhood. In addition, living with a non-sibling in extended-family homes may contribute to infection risk but only in households with prevalent H. pylori infection within all family groups.