OBJECTIVE: To determine the burden and impact of immune reconstitution disease (IRD) associated with tuberculosis (TB) among patients initiating antiretroviral treatment (ART) in sub-Saharan Africa. DESIGN: Retrospective analysis of a study cohort enrolled over 3 years within a community-based ART service in South Africa. METHODS: Patients receiving treatment for TB at the time ART was initiated (n = 160) were studied. Cases of TB-associated IRD during the first 4 months of ART were ascertained. RESULTS: The median baseline CD4 cell count was 68 cells/microl [interquartile range (IQR), 29-133 cells/microl) and ART was initiated after a median of 105 days (IQR, 61-164 days) from TB diagnosis. Although IRD was diagnosed in just 12% (n = 19) of patients overall, IRD developed in 32% (n = 12) of those who started ART within 2 months of TB diagnosis. Pulmonary involvement was observed in 84% (n = 16) and intra-abdominal manifestations were also common (37%). Overall, 4% (n = 7) of the cohort required secondary level health-care for IRD and two (1%) patients died. In multivariate analysis, risk of IRD was strongly associated with early ART initiation and low baseline CD4 cell count. Of patients with CD4 counts < 50 cells/microl, the proportions who developed IRD following initiation of ART within 0-30, 31-60, 61-90, 91-120 and > 120 days of TB diagnosis were 100%, 33%, 14%, 7% and 0%, respectively. CONCLUSIONS: The risk of TB-associated IRD in this setting is very high for those with low baseline CD4 cell counts initiating ART early in the course of antituberculosis treatment. However, most cases were self-limiting; overall secondary health-care utilization and mortality risk from IRD were low.