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Background: For anorexia nervosa, firm evidence of the superiority of specialized psychological treatments is limited and economic evaluations of such treatments in real world settings are scarce. This consecutive cohort study examined differential (cost-)effectiveness for adult inpatients and outpatients with anorexia nervosa, after implementing cognitive behavioral therapy-enhanced (CBT-E) throughout a routine setting. Methods: Differences in remission, weight regain and direct eating disorder treatment costs were examined between one cohort (N = 75) receiving treatment-as-usual (TAU) between 2012–2014, and the other (N = 88) CBT-E between 2015–2017. The economic evaluation was performed from a health care perspective with a one-year time horizon, using EDE global score < 2.77, the absence of eating disorder behaviors combined with a BMI ≥ 18.5, as effect measure. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were displayed to assess the probability that CBT-E is cost effective compared to TAU. Results: Using direct eating disorder treatment costs in the cost-effectiveness analysis, the cost-effectiveness plane of the base case scenario for all patients indicated a 84% likelihood of CBT-E generating better health gain at additional costs. The median ICER is €51,081, indicating a probable preference for CBT-E (> 50% probability of cost-effectiveness) assuming a WTP of €51,081 or more for each additional remission, On remission, no difference was found with 9.3% remission during TAU and 14.6% during CBT-E (p =.304). Weight regain was higher during CBT-E (EMD = 1.33 kg/m2, SE =.29, 95% CI [0.76–1.9], p <.001). Conclusions: In this mixed inpatient and outpatient cohort study, findings indicate a probability of CBT-Ebeing more effective at higher costs. These findings may contribute to the knowledge of effectiveness and cost-effectiveness of specialized psychological treatments. Plain English Summary: In this study, the effectiveness and treatment costs of a specialized psychological treatment for adult clients with anorexia nervosa were compared with a regular, non-specialist treatment. One group of inpatients and outpatients did receive non-specialist treatment, the next group of inpatients and outpatients received CBT-E, a specialized treatment, later on. CBT-E is recommended for clients with bulimia and with binge eating disorder, for clients with anorexia nervosa it is less clear which specialized psychological treatment should be recommended. Results indicate that at end-of-treatment, CBT-E was not superior on remission. When looking at weight regain, CBT-E seemed superior than the treatment offered earlier. Economic evaluation suggests that CBT-E generates better health gain, but at additional costs. This study contributes to the knowledge on the effectiveness and treatment costs of psychological treatments, as they are offered in routine practice, to adults with anorexia nervosa. [ABSTRACT FROM AUTHOR]