BACKGROUND & AIMS Symptoms of Inflammatory Bowel Disease (IBD) include bloody diarrhea, fatigue, abdominal pain and weight loss. Long-term management of remission for most patients requires adherence to taking one or more oral medications daily, in the absence of symptoms. We investigated whether disease characteristics and behavioral characteristics predict adherence to prescribed medical regimes. METHODS Patients 8 to 17.5 years of age, newly diagnosed with IBD as well as a matched cohort previously diagnosed were studied over a 6-month period. Adherence was assessed using medication electronic monitoring devices (MEMS); participants and parents completed questionnaires regarding emotional and behavioral functioning, and biological parameters were monitored. RESULTS Adherence was monitored for 45 newly and 34 previously diagnosed patients. In total, 16,478 patient days (including 12,066 discrete days) were electronically monitored. Overall 70.6% of 5-ASA and 65.4% of 6-MP doses were taken. Only 25% and 15% of older adolescents took at least 80% of their 5-ASA and 6-MP, respectively, compared to about 83% and 64% of 8–11 year-olds. Only age and behavioral issues were statistically linked to rates of adherence. CONCLUSIONS Adherence to commonly prescribed oral medications for IBD is challenging for patients. Screening for emotional and behavioral problems, especially among older adolescents, would be important in identifying patients at risk for poor adherence, who might benefit from interventions. Biological solutions, while critical, when applied without attention to behavioral issues, are not likely to provide the level of therapeutic benefit that can be provided in a combined bio-behavioral approach.