BACKGROUND: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared. METHODS: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling. RESULTS: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. CONCLUSIONS: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.