OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P </= 0.001) and decreasing CD4 cell counts (chi for trend = 72.4, P </= 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status. CONCLUSIONS: Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death.