Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive risperidone (n = 18) or placebo (n = 22). Subjects completed the Eating Disorder Inventory 2, Color-A-Person Test, Body Image Software, and Multidimensional Anxiety Scale for Children at baseline and regular intervals. Weight, laboratory values, and electrocardiograms were monitored. Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5-mg increments to a maximum dose of 4 mg until the subject reached a study endpoint. Results: The mean dose for the risperidone group was 2.5 mg and for the placebo group was 3 mg for a mean duration of 9 weeks. Subjects taking risperidone had a significant decrease on the Eating Disorder Inventory 2 Drive for Thinness subscale over the first 7 weeks (effect size, 0.88; p = 0.002), but this difference was not sustained to the end of the study (p = 0.13). The Eating Disorder Inventory 2 Interpersonal Distrust subscale decreased significantly more in subjects taking risperidone (effect size, 0.60; p = 0.03). Subjects taking risperidone had increased prolactin levels (week 7; p = 0.001). There were no significant differences between groups at baseline or the end of the study for the other rating scales, change in weight, or laboratory measurements. Conclusions: This study does not demonstrate a benefit for the addition of risperidone in adolescents with anorexia nervosa during the weight-restoration phase of care. Clinical trial registration information: A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Anorexia Nervosa, NCT00140426. (Contains 2 figures and 3 tables.)