Pomegranate juice (PJ; also known as pomegreat pure juice) provides a rich and varied source of polyphenolic compounds that may offer cardioprotective, anti-atherogenic and antihypertensive effects. The aim of this study was to investigate the effect of PJ consumption on glucocorticoids levels, blood pressure (BP) and insulin resistance in volunteers at high CVD risk. Subjects (twelve males and sixteen females) participated in a randomised, placebo-controlled cross-over study (BMI: 26·77 (sd 3·36) kg/m2; mean age: 50·4 (sd 6·1) years). Volunteers were assessed at baseline, and at weeks 2 and 4 for anthropometry, BP and pulse wave velocity. Cortisol and cortisone levels in urine and saliva were determined by specific ELISA methods, and the cortisol/cortisone ratio was calculated. Fasting blood samples were obtained to assess plasma lipids, glucose, insulin and insulin resistance (homeostasis model assessment of insulin resistance). Volunteers consumed 500 ml of PJ or 500 ml of a placebo drink containing a similar amount of energy. Cortisol urinary output was reduced but not significant. However, cortisol/cortisone ratios in urine (P = 0·009) and saliva (P = 0·024) were significantly decreased. Systolic BP decreased from 136·4 (sd 6·3) to 128·9 (sd 5·1) mmHg (P = 0·034), and diastolic BP from 80·3 (sd 4·29) to 75·5 (sd 5·17) mmHg (P = 0·031) after 4 weeks of fruit juice consumption. Pulse wave velocity decreased from 7·5 (sd 0·86) to 7·44 (sd 0·94) m/s (P = 0·035). There was also a significant reduction in fasting plasma insulin from 9·36 (sd 5·8) to 7·53 (sd 4·12) mIU/l (P = 0·025) and of homeostasis model assessment of insulin resistance (from 2·216 (sd 1·43) to 1·82 (sd 1·12), P = 0·028). No significant changes were seen in the placebo arm of the study. These results suggest that PJ consumption can alleviate key cardiovascular risk factors in overweight and obese subjects that might be due to a reduction in both systolic and diastolic BP, possibly through the inhibition of 11β-hydroxysteroid dehydrogenase type 1 enzyme activity as evidenced by the reduction in the cortisol/cortisone ratio. The reduction in insulin resistance might have therapeutic benefits for patients with non-insulin-dependent diabetes, obesity and the metabolic syndrome.