Abstract Objective To determine what predicts initial and sustained weight loss in subjects consuming a reduced-fat diet ad libitum and the relationship between achieved level of fat intake and weight loss. Design Placebo arm of a randomized, controlled trial of a weight-loss drug (dexfenfluramine) in the context of an ad libitum, reduced-fat, diet. Subjects Thirty-nine subjects (initial mean body mass index±standard deviation=34.9±3.4; body mass index is calculated as kg/m 2) from the placebo group who completed the 9-month study. Intervention Dietary assessment and education (month 0) followed by monthly meetings during the single intervention of reducing fat intake (months 1 through 6); one follow-up at 9 months. Main outcome measures Initial weight loss (first 3 months) and sustained weight loss (over 9-month period). Statistics Dietary intake, body size, exercise levels, age, and gender were included in multiple regression linear models of initial and sustained weight loss if they were significant independent predictors. Results Greater initial weight loss was associated with a greater decrease in fat intake and a lower achieved fat intake at 3 months. Greater sustained weight loss was associated with a lower achieved fat intake, a higher baseline waist circumference, and higher moderate-intensity exercise levels (months 3 and 6). Weight loss occurred in all subjects who reported a fat intake of 40 g/day or less. Applications The obese persons most likely to achieve and sustain weight loss on an ad libitum, reduced-fat diet are those who can substantially reduce fat intake, those with high initial levels of abdominal fat, and those who undertake regular moderate-intensity exercise. A target of less than 40 g fat per day might be an appropriate goal to ensure weight loss, but dietary underreporting and the difficulty of sustaining very-low-fat intakes need to be considered. J Am Diet Assoc. 1998;98:35-39.