BACKGROUND: Inflammatory bowel diseases (IBDs) are increasingly recognized as products of the brain-gut axis associated with dysfunctions of the chronic stress response systems. The objectives of this study were to evaluate the feasibility, acceptability, and preliminary efficacy of a virtual, group-based heart rate variability (HRV) biofeedback-enhanced coping skills intervention for youth with IBD. Treatment targets included symptoms of anxiety, depression, gastrointestinal (GI) symptoms, and perceived stress. METHODS: Youth with IBD (ages 13-18) and their caregivers were randomized to either immediate treatment or waitlist control groups. The intervention consisted of 6 virtually delivered, weekly group sessions combining cognitive-behavioral therapy (CBT) with HRV biofeedback training. Outcomes included measures of anxiety, depression, GI symptoms, perceived stress, and HRV parameters. Assessments were conducted at baseline and post-intervention. RESULTS: Of the 53 youth randomized, 50 participated in their assigned group. The intervention demonstrated strong feasibility with 84% of participants attending at least 4 of 6 sessions. Both adolescents and parents reported strong satisfaction. Following treatment, parents reported significant decreases in adolescent depressive symptoms, anxiety symptoms, and GI symptoms compared to controls. Adolescents reported reductions in GI symptoms and perceived stress compared to controls and reductions in symptoms of anxiety within the treatment group. No changes were observed in HRV parameters. CONCLUSIONS: This pilot study supports the feasibility and acceptability of a virtual, group-based HRV biofeedback-enhanced coping skills intervention for youth with IBD. Preliminary efficacy was demonstrated for reducing psychological and physical symptoms. Future research should evaluate efficacy in a larger, more diverse sample with elevated baseline psychological symptoms.