CONTEXT: Long-term success in weight loss with dietary treatment has been elusive. OBJECTIVE: To evaluate a diet moderate in fat based on the Mediterranean diet compared to a standard low-fat diet for weight loss when both were controlled for energy. DESIGN: A randomized, prospective 18 month trial in a free-living population. PATIENTS: A total of 101 overweight men and women (26.5 -46 kg=m 2 ). INTERVENTION: (1) Moderate-fat diet (35% of energy); (2) low-fat diet (20% of energy). MAIN OUTCOME MEASUREMENTS: Change in body weight. RESULTS: After 18 months, 31=50 subjects in the moderate-fat group, and 30=51 in the low fat group were available for measurements. In the moderate-fat group, there were mean decreases in body weight of 4.1 kg, body mass index of 1.6 kg=m 2 , and waist circumference of 6.9 cm, compared to increases in the low-fat group of 2.9 kg, 1.4 kg=m 2 and 2.6 cm, respectively; P 0.001 between the groups. The difference in weight change between the groups was 7.0 kg. (95% CI 5.3, 8.7). Only 20% (10=51) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54% (27=50) in the moderate-fat group, (P < 0.002). The moderate-fat diet group was continued for an additional year. The mean weight loss after 30 months compared to baseline was 3.5 kg (n ¼ 19, P ¼ 0.03). CONCLUSIONS: A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.