Objective: To compare the effects of two energy-restricted healthy diets, one with a low GI and one with a high GI, on heart disease risk factors and weight loss in subjects at risk of heart disease. Design: A12-week randomized parallel study of low and high GI, healthy eating diets was carried out. Setting: The study was carried out at the Hammersmith Hospital. Subjects: Eighteen subjects were recruited by advertisement and randomized to one of the two diets. Fourteen completed the study but one was excluded from the final analysis. Methods: At randomization, subjects were advised to follow the intervention diet for 12 weeks. Before randomization and on completion of the study, anthropometrics, fasting cholesterol and glucose blood tests and 24-h glucose measurements were taken using a continuous glucose monitoring system (CGMS). Statistical analysis was carried out using non-parametric tests. Median (IQR) are presented. Results: A significantly different dietary GI was achieved in the low GI (median: 51.3 (IQR: 51.0-52.0) compared to the high GI (59.3 (59.2-64.0) (P=0.032) group. By week 12, both groups reduced their energy intake by: low GI group: -167 (-312--123) kcal/day (P=0018) vs high GI group: -596 (-625- -516) (P=0.018) kcal/day, the difference between the groups being significant (P=0.010). However, only the low GI group lost weight (-4.0 (-4.4--2.4)kg (P=0.018) whereas the high GI group did not significantly change in weight (-1.5 (-3.6-0.8)kg (P=0.463). By week 12, the low GI group also had a significantly lower 24-h area under the curve (AUC) (7556 (7315-8434) vs 8841 (8424-8846) mmol-h/l (P=0.045) and overnight AUC (2429 (2423-2714) vs 3000 (2805-3072) mmol-h/l (P=0.006) glucose as measured by CGMS. There were no differences in the other heart disease risk factors assessed. Conclusions: This pilot study provides some evidence that consuming a low GI diet in addition to weight loss and healthy eating may reduce cardiovascular risk. Other potential benefits of GI might have been masked by weight loss in the low GI group. Larger-scale studies need to follow.