The purpose of this study was to examine the relationship of oral medication adherence and perceived adherence barriers with disease severity in a sample of adolescents with inflammatory bowel disease (IBD). Participants included 62 adolescents, aged 13-17 years, diagnosed with IBD, and their parents. Data on the measures of parent-rated and patient-rated oral medication adherence and related barriers, behavioral and emotional functioning per parent report and self-report, and disease severity per medical chart reported by a physician were obtained. Fifteen percent of the sample reported clinically elevated depressive symptoms and 24% reported clinically elevated internalizing behavioral problems. Number of reported adherence barriers was 2.6±1.5, and none of the participants reported zero barriers. Parental ratings of medication adherence (t = -2.11, P<0.05) and perceived barriers to adherence (t = 2.05, P<0.05) significantly predicted disease severity after statistically controlling for the contributions of behavioral and disease parameters to disease severity. Results suggest that the oral medication adherence and perceived adherence barriers are significantly related to disease severity in adolescents with IBD. These patients also may be at risk for increased behavioral and emotional problems, which may impact health outcomes as well. Clinicians should make particular efforts to attend to medication adherence issues with their patients. Working with patients and families to develop solutions for eliminating adherence barriers might result in better disease outcomes.