Anxiety is a prevalent and impairing psychiatric condition among children and adolescents with inflammatory bowel disease (IBD). Despite the need for effective treatment, no studies have examined the benefit of cognitive-behavioral therapy (CBT) for anxiety disorders among children or adults with IBD. The aim of this paper is twofold: (a) to briefly describe a newly adapted CBT protocol, treatment of anxiety and physical symptoms related to IBD (TAPS + IBD), that concurrently addresses anxiety (including IBD-specific anxiety) and disease management among children and adolescents with IBD in pediatric medical offices; and (b) to present initial pilot data examining the feasibility and potential efficacy of TAPS + IBD compared to nondirective supportive therapy (NDST) among youth with comorbid IBD and anxiety. Twenty-two youth (59% female; mean age 13.2 ± 2.1) with comorbid IBD and anxiety disorder were randomly assigned to a 13-session TAPS + IBD or NDST program. Following treatment, participants in TAPS + IBD demonstrated higher treatment response rates relative to the NDST control treatment. Compared with NDST, TAPS + IBD was associated with significantly greater reductions in IBD-specific anxiety immediately following treatment and 3 months later. TAPS + IBD shows initial promise for the treatment of anxiety in youth with IBD. The direct integration of behavioral health strategies into medical settings and use of a flexible CBT approach sensitive to acute disease fluctuations appears to be beneficial among youth with comorbid IBD and anxiety.