This observational study examined the changes during inpatient cognitive-behavioral treatment (CBT) of adolescents with chronic anxious-depressive school absenteeism with or without comorbid disruptive symptoms. 147 adolescents (aged 12-18 years) with a specific phobia or other anxiety disorder or a depressive episode or a mixed disorder of conduct and emotions and who had completely ceased to attend school or showed irregular school attendance underwent an inpatient cognitive-behavioral treatment. A further 16 patients aborted the treatment during the first day and were not included in the analyses. The treatment was manual guided and also included parents. Assessments were made pre-inpatient treatment, immediately post-inpatient treatment and at 2-month follow-up. School attendance was the primary outcome variable and secondary outcomes were composite scores of a range of adolescent- and parent-rated mental health problems. Overall, results show a considerable decline of school absenteeism and mental health problems during treatment and subsequent follow-up. Continuous school attendance was achieved by 87.1% of the sample at the end of inpatient treatment and by 82.3% at 2-month follow-up. Comorbid symptoms of anxiety, depression, disruptive and insufficient learning behavior were significantly reduced from pre to follow-up, with effect sizes for the composite scores ranging from 0.44 to 1.15 (p < 0.001). This large observational study in adolescents with school absenteeism and a mixture of emotional and disruptive symptoms is the first to show the benefits of inpatient therapy that included cognitive-behavioral therapy and access to a special school with expertise on teaching children and adolescents with psychiatric disorders. The results must be interpreted conservatively because of the lack of a control condition.