This study evaluated the clinical significance as well as predictors of outcome for adolescents with severe anorexia nervosa (AN) treated in an inpatient setting. Body mass index (BMI), eating disorder (ED) symptoms [Eating Disorder Inventory‐2 (EDI‐2)], general psychopathology and depression were assessed in 238 patients at admission and discharge. BMI increased from 14.8 + 1.2 to 17.3 + 1.4 kg/m2. Almost a fourth (23.6%) of the patients showed reliable changes, and 44.7% showed clinically significant changes (EDI‐2). BMI change did not significantly differ between those with reliable or clinically significant change or no reliable change in EDI‐2. Length of stay, depression and body dissatisfaction were negative predictors of a clinically significant change. Inpatient treatment is effective in about two thirds of adolescents with AN and should be considered when outpatient treatment fails. About one third of patients showed significant weight gain, but did not improve regarding overall ED symptomatology. Future studies should focus on treatment strategies for non‐responders. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.