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In the current context of dyslipidaema, hyperglycaema and lipodystrophia observed among HIV-seropositive subjects, it is important to study the risk of myocardial infarction (MI) in this population. The French Hospital Database on HIV, which includes a large number of seropositive subjects followed for substantial periods, offers the opportunity to analyse the impact of protease inhibitors (PI) on the risk of MI among men.Cox model was used to study the risk factors of MI occurrence. Standardized morbidity ratios (SMR) in men exposed to PI were calculated with data from the French general male population (FGMP) of the same age as reference.Between 1996 and 1999, MI was diagnosed in 60 men among 88 029 person-years (PY), including 49 cases among men exposed to PI. In the Cox model, exposure to PI was associated with a higher risk of MI [relative hazard (RH), 2.56; 95% confidence interval (CI), 1.03–6.34]. The expected incidence in the FGMP was 10.8/10 000 PY. The SMR relative to the FGMP was 0.8 (95% CI, 0.5–1.3) for men exposed to PI for < 18 months (G1), 1.5 (95% CI, 0.8–2.5) for men exposed for 18–29 months (G2) and 2.9 (95% CI, 1.5–5.0) for men exposed for ≥ 30 months (G3). With G1 as reference, the SMR was 1.9 (95% CI, 1.0–3.1) for G2 and 3.6 (95% CI, 1.8–6.2) for G3.Our results point to a duration-related effect relationship between PI and MI, with a higher MI incidence rate among men exposed to PI for 18 months or more.