Objective: For children with problematic severe asthma, achieving adequate control of asthma is difficult. The aim of this prospective observational study was to evaluate the effects of intensive multidisciplinary inpatient treatment on multiple outcome variables in children with problematic severe asthma. Methods: Participants were 89 children with problematic severe asthma (mean age 13.6 ± 2.5 years) treated in tertiary care clinics at high altitude (Switzerland) or sea level (Netherlands) and their parents (85 mothers, 55 fathers). The primary outcome variable was the Childhood Asthma Control Test (C-ACT). Other outcome variables were forced expiratory volume in 1 sec (FEV1), fractional concentration of exhaled nitric oxide (FeNO), quality of life [PAQLQ(S)], children's coping (UCL-A), parents’ report of behavioral problems (CBCL), and parenting stress (PSI/NOSI). Evaluations were taken pre-treatment, post-treatment, and 3–6 months follow-up. Median [P25;P75] treatment duration 74 [56;80] days; Median follow-up interval 131 [103;177] days. Results: The percentages of children showing controlled asthma (C-ACT) were 18% (pre-treatment), 69% (post-treatment), and 44% (follow-up). The vast majority of the children (80%) showed an improvement on C-ACT with 4% showing a deterioration. On C-ACT, FeNO, quality of life, and behavioral problems, improvements at post-treatment were highly significant. Improvements generally remained at a functional level at follow-up. Children's coping and parenting stress in parents did not change. Conclusions: The improvement in asthma control and other outcome variables suggests that multidisciplinary inpatient treatment is an effective approach for a heterogeneous group of children with asthma that remained uncontrolled in secondary care. Pediatr Pulmonol. 2017;52:588–597.