Objective: To examine the feasibility and efficacy of a manual-based cognitive-behavioral therapy (CBT) in reducing depressive symptomatology in adolescents with inflammatory bowel disease (IBD). Primary and Secondary Control Enhancement Therapy-Physical Illness(PASCET-PI) modified for youths with IBD was compared to treatment as usual (TAU), plus an information sheet about depression, without therapist contact using assessable patient analysis. Method: Following assessment, participants 11 to 17 years old with IBD and mild to moderate subsyndromal depression were randomly assigned to PASCET-PI (n = 22) or comparison treatment (n = 19). Primary outcome measures at baseline (T1) and 12 to 14 weeks posttreatment (T2) were Children's Depression Inventory (child/parent report), Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), Children's Global Assessment Scale, and Perceived Control Scale for Children. Results: The PASCET-PI group showed significantly greater improvement in Children's Depression Inventory (child/parent report), Children's Global Assessment Scale, and Perceived Control Scale for Children posttreatment than the comparison group. Conclusions: Screening and treatment of depressive symptoms in pediatric settings is feasible. PASCET-PI may be an efficacious intervention for subsyndromal depression in adolescents with IBD, although comparison with a more active treatment is necessary to attribute the improvement to PASCET-PI. (Contains 3 tables and 1 figure.) [Funding for this study was provided in part by the Wolpow Family Fund.]