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The present study aimed to investigate the effectiveness of a 3-week multimodal inpatient pain program for children and adolescents with chronic pain.Effectiveness was investigated for pain-related variables (pain intensity, pain-related disability) and emotional distress in 3 ways: (1) in terms of statistically significant changes; (2) in terms of the clinical significance of these changes by creating post-hoc outcome groups for pain-related variables and emotional distress; and (3) in terms of the clinically significant overall amelioration generalizing the outcome over 3 variables (ie, pain intensity, pain-related disability, and school absence). One hundred sixty-seven adolescents (aged between 11 and 18 y) with various pain disorders (50% with headache) who met inpatient criteria were evaluated at baseline and 3 months posttreatment.Patients demonstrated statistically significant changes in all variables with large to medium effect sizes. Seventy-two percent and 45% of the patients demonstrated clinically significant changes in pain intensity and pain-related disability, respectively. The percentages of patients demonstrating clinically significant change in emotional distress ranged from 13% to 26%. Seventy-seven adolescents demonstrated overall amelioration.Results of the study are promising in at least 2 ways: (1) a multimodal inpatient program might stop the negative effects of chronic pain, disability, and emotional distress in children and adolescents, and (2) the exploration of clinical significance testing has demonstrated utility and can be applied to future effectiveness studies in pediatric pain.