Background: Chronic inflammation in Crohn’s disease (CD) often leads to complications such as fistulae and strictures. Further, 85% of people with CD will be hospitalized at least once in 5 years and 18% will require surgery within 5-years. Immune-modifying medications can decrease the likelihood of these downstream complications. Despite widespread availability of these drugs and a growing recognition of their value among gastroenterologists, approximately 40% of patients do not comply with optimized maintenance regimens for CD. Disease morbidity is markedly increased in medication non-adherent CD patients. Untreated CD results in increased rates of hospitalizations, disability, complications, and colon cancer, and decreased quality of life. Given the current dearth of literature surrounding medication decision-making, we sought to identify the factors that motivate adherence or non-adherence with immune modifying medications for CD. Methods: We conducted qualitative interviews in people with CD who were identified as adherent or non-adherent to immune-modifying medication recommendations by their treating gastroenterologist. Semi-structured interview guides were developed based on the Theoretical Domains Framework (TDF), an established framework for understanding barriers and facilitators of health behaviors. We conducted content analysis of the resulting qualitative data using a blended inductive-deductive approach to identify emergent themes that influence medication decision-making. Results: Twenty-four patients with CD completed interviews for this study. Interviews were independently coded and analyzed for themes. Two broad domains emerged comprising: 1) themes reflected in the TDF, and 2) novel themes specific to medication decision-making in CD. Themes specific to medication decision-making included knowledge about CD, beliefs about the consequences of medication use or non-use, prior experiences with medications, discomfort with uncertainty, strength of the patient-provider relationship, and overall disease acceptance. Adherent patients conveyed a sense of trust in science and healthcare provider expertise, while non-adherent patients were more likely to express beliefs in their ability to self-manage CD, concern about risks associated with medication, and a general ambivalence to treatment. Conclusion(s): There are clear cognitive, behavioral and relational factors that guide patients’ medication-related decision-making. Thus, it is likely that patients who are non-adherent to medication recommendations could benefit from an intervention designed to target these specific factors. A population-specific behavioral intervention will be paramount for improving medication adherence in people with CD at high-risk for complications, and would be an impactful tool for improving both disease-related outcomes and quality of life. A mechanism for early identification of potentially non-adherent patients in conjunction with a behavioral intervention to improve adherence has the potential to prevent the development of CD complications and decrease CD-associated morbidity.