Background: Individuals with eating disorders show deficits in neuropsychological functioning which might preexist and underlie the etiology of the eating disorders and influence relapse. Deficits in cognitive flexibility, i.e. set-shifting and central coherence, might perpetuate the symptoms. Cognitive remediation therapy (CRT) was developed to improve cognitive flexibility, thereby increasing the likelihood of improved outcome. The focus of CRT is on how patients think, rather than on what patients think. The present study investigated the effectiveness of CRT for patients with a severe or enduring eating disorder by means of a randomized controlled trial comparing intensive treatment as usual (TAU) to CRT plus TAU. Methods: Eighty-two patients were randomly assigned to CRT plus TAU (n = 41) or TAU alone (n = 41). Outcome measures were set-shifting, central coherence, eating disorder and general psychopathology, motivation, quality of life and self-esteem. Assessments were performed at baseline (n = 82) and after 6 weeks (T1; n = 75) and 6 months (T2; n = 67). Data were analyzed by means of linear mixed model analyses. Results: Patients who received CRT in addition to TAU improved significantly more with regard to eating disorder-related quality of life at the end of treatment (T1) and eating disorder psychopathology at follow-up (T2), compared to those who received TAU only. Moreover, moderator analyses revealed that patients with poor baseline set-shifting abilities benefited more from CRT than patients with no deficits in set-shifting abilities at baseline; the quality of life of the former group was higher than that of the latter at follow-up. Conclusions: CRT seems to be promising in enhancing the effectiveness of concurrent treatment.