OBJECTIVE: To estimate the incidence of serum hypertriglyceridaemia > 6 mm/L (HTG) and identify associated factors in the era of highly active antiretroviral therapy (HAART). METHODS: A prospective cohort, multirisk, both genders, of HIV-infected patients was treated with several patterns of antiretrovirals. Cox's model was used to estimate the effect of explanatory variables documented at the first normal triglyceride measurement (< 2 mm/L) on the subsequent occurrence of HTG. RESULTS: Among 925 patients (27% treated with a protease inhibitor (PI) containing regimen and 48% treated with other HAART combinations) followed 25 months in median with a median triglyceridaemia of 1.1 mm/L at baseline, 70 experienced an HTG, 4.2 cases per 100 person years[95% confidence interval (CI)=2,2,3,3-5]. Univariate analysis retained the following as risk factors of HTG: male gender, homosexual transmission group, greater age, higher body weight, AIDS stage, > or = 2 antiretrovirals including PI, higher triglyceride level and lower CD4+ cell count at baseline. In multivariate analysis, the risk of HTG remained associated with being male homosexual [hazard ratio (HR) = 1.68, P = 0.04], at the AIDS stage (HR = 1.84, P = 0.03), with increased triglyceride level (HR = 2.82 for 1 mm/L higher at baseline, P < 10-3), impaired CD4+ cell count (HR = 1.2 for 100 cells/microL lower, P = 0.02) and increased body weight (HR = 1.3 for 10 kg higher, P = 0.02). CONCLUSIONS: Baseline triglyceride level and being overweight are risk factors of HTG, together with advanced HIV disease, but the contribution of HAART is not demonstrated.