Angiotensin-converting enzyme inhibitors (ACEIs) are used in the management of a range of cardiovascular disorders and are well established in primary as well as secondary cardiovascular prevention programmes. Over the years, several second- and third-generation ACEIs have been introduced into the clinic. In a comparative study in patients with mild to moderate hypertension, the efficacy and safety of zofenopril 30 mg od (with an up-titration to 60 mg od after 4 weeks in non-responder patients) was compared with enalapril 20 mg od (with an up-titration to 40 mg od after 4 weeks in nonresponders) during 12 weeks of treatment. Both treatments significantly reduced systolic (SBP) and diastolic blood pressure (DBP). BP reduction was significantly greater with zofenopril (30 mg/day) during the initial 4 weeks of treatment compared with enalapril (20 mg/day). A larger proportion of patients needed dose up-titration with enalapril compared with zofenopril to reach preset BP goals. After 12 weeks of treatment and after appropriate dose up-titration, SBP and DBPs were lowered to similar extent in the two treatment groups, resulting in no differences between the groups in terms of response and control rates. A similar number of patients reported adverse events in the two study groups. However, the severity of adverse events were significantly milder with zofenopril compared with enalapril. In mild to moderate hypertensive patients, zofenopril treatment results in a more pronounced lowering of BP compared with enalapril at recommended dose levels. Additionally, at clinical and comparative antihypertensive doses, zofenopril presents a more beneficial adverse event profile compared with enalapril.