Two hundred and twelve HIV-positive patients who started a new protease inhibitor (PI)-based antiretroviral regimen between January 1998 and December 2000 in our tertiary care centre were prospectively followed-up during a 12-month study period, in order to assess the incidence of hyperlipidaemia and related clinical adverse events. At the end of 1-year follow-up, PI-containing antiretroviral treatment led to a statistically significant increase in serum triglyceride levels (P<0.005) and total and LDL-cholesterol levels (P<0.05). The overall incidence of hypertriglyceridaemia and hypercholesterolaemia was 38.2 and 25%, respectively. The incidence of increased serum triglyceride levels was significantly higher in patients treated with ritonavir (66.6%) or lopinavir/ritonavir (60.7%), compared with other PIs (P<0.04). Clinical adverse events possibly related to the hyperlipidaemia (such as cardiovascular diseases or acute pancreatitis) were not observed during the entire 12 months study period. In conformity with other previously published studies, the very high incidence of hyperlipidaemia during a PI-based therapy recognised in our work raises a big concern about its potential clinico-pathological consequences and the most convenient pharmacological management of these metabolic imbalances.