To evaluate the clinical efficacy of early angiotensin-converting enzyme (ACE) inhibition by zofenopril in patients with anterior myocardial infarction and normal or high plasma low density lipoprotein-cholesterolaemia. Post hoc analysis of the Survival of Myocardial Infarction Long-Term Evaluation study, a double-blind, clinical trial including 1400 patients with anterior myocardial infarction, randomized to zofenopril (n = 699, 66% hypercholesterolemics) or placebo (n = 701, 64% hypercholesterolemics) for 6 weeks. The rate of the primary end-point (6-week combined occurrence of death and severe congestive heart failure) was 8.1% in hypercholesterolemic and 6.4% in normocholesterolemic patients (P < 0.03). The favourable effect of treatment with zofenopril was enhanced in hypercholesterolemics patients when compared with normocholesterolemics (RRR = 43%, P = 0.034 vs. 25%, P = 0.19). One-year mortality was 10% in hypercholesterolemic patients vs. 7.5% in normocholesterolemic patients (P = 0.037), equally reduced in both hypercholesterolemic and normocholesterolemics patients by zofenopril. The presence of hypercholesterolaemia in patients with anterior myocardial infarction could be associated with more favourable effects of early ACE-inhibition.