Endothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a double-blind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m2) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.