It is increasingly accepted that more intensive lipid-lowering treatment is associated with greater cardiovascular risk reductions in patients with coronary heart disease (CHD), thus providing a rationale for more aggressive LDL-cholesterol (LDL-C) targets. Ezetimibe in combination with statin therapy provides an additional approach to lipid management by utilising the additive action of two different mechanisms of LDL-C reduction. In this multicentre, randomised, double-blind, placebo-controlled study, a total of 98 men and 55 women with CHD and primary hypercholesterolaemia, naïve to statin therapy, were randomised to receive treatment for 6 weeks with either ezetimibe 10 mg–simvastatin 20 mg (n = 77) or placebo–simvastatin 20 mg (n = 75). At 6 weeks, ezetimibe 10 mg–simvastatin 20 mg provided a mean additional LDL-C reduction of 14.6% (95% CI 10.1–19.1) compared with simvastatin monotherapy (p < 0.0001). Moreover, a higher proportion of patients on ezetimibe/simvastatin achieved the National Standard Framework LDL-C standard (<3.0 mmol/l; 93% vs. 75%, p < 0.001) or the new Joint British Societies (JBS 2) goal of LDL-C < 2.0 mmol/l (49.3% vs. 11.1%, p < 0.001). On logistic regression analysis, the odds ratio of achieving target LDL-C with ezetimibe 10 mg–simvastatin 20 mg was 5.1 (95% CI 1.8–15.0) times higher than with simvastatin monotherapy (p = 0.003). Clinical chemistry profiles and proportions of adverse events were similar in both groups at baseline and follow-up. In conclusion, ezetimibe 10 mg–simvastatin 20 mg is a practical, effective and safe option for the treatment of primary hypercholesterolaemia in CHD patients, and brings more patients to new aggressive cholesterol targets compared with simvastatin 20 mg monotherapy.