To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged < 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants. The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004-2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates. The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361-1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587-2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377-1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567-1495) per 100 000. Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk-benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.