Theoretical calculations suggest that small daily reductions in energy intake can cumulatively lead to substantial weight loss, but experimental data to support these calculations are lacking. We conducted a 1-year randomized controlled pilot study of low (10%) or moderate (30%) energy restriction (ER) with diets differing in glycemic load in 38 overweight adults (mean ± s.d., age 35 ± 6 years; BMI 27.6 ± 1.4 kg/m2). Food was provided for 6 months and self-selected for 6 additional months. Measurements included body weight, resting metabolic rate (RMR), adherence to the ER prescription assessed using 2H218O, satiety, and eating behavior variables. The 10%ER group consumed significantly less energy (by 2H218O) than prescribed over 12 months (18.1 ± 9.8%ER, P = 0.04), while the 30%ER group consumed significantly more (23.1 ± 8.7%ER, P < 0.001). Changes in body weight, satiety, and other variables were not significantly different between groups. However, during self-selected eating (6–12 months) variability in % weight change was significantly greater in the 10%ER group (P < 0.001) and poorer weight outcome on 10%ER was predicted by higher baseline BMI and greater disinhibition (P < 0.0001; adj R2 = 0.71). Weight loss at 12 months was not significantly different between groups prescribed 10 or 30%ER, supporting the efficacy of low ER recommendations. However, long-term weight change was more variable on 10%ER and weight change in this group was predicted by body size and eating behavior. These preliminary results indicate beneficial effects of low-level ER for some but not all individuals in a weight control program, and suggest testable approaches for optimizing dieting success based on individualizing prescribed level of ER.