BACKGROUND: This study examined the relationship between psychological inflexibility, internalized stigma, and patient outcomes in adults with inflammatory bowel disease (IBD). It aimed to explore if psychological inflexibility mediated the relationship between internalized stigma and patient outcomes. METHODS: Three hundred and eighty-two participants with IBD took part in a cross-sectional quantitative study conducted via an online survey from May to December 2020. Participants completed questionnaires that assessed psychological inflexibility, committed action, internalized stigma related to IBD, psychological distress, IBD self-efficacy, self-concealment, beliefs about emotions, and fatigue. Participants also completed a sociodemographic and clinical questionnaire in addition to a bespoke Covid-19 questionnaire. Pearson's correlations and exploratory simple mediation analyses were used to examine relationships between variables and the mediating effect of psychological inflexibility. RESULTS: 40.5% of participants experienced internalized stigma. Higher psychological inflexibility was associated with higher internalized stigma, lower committed action, poorer health-related quality of life, lower IBD self-efficacy, higher self-concealment, higher fatigue, and more negative beliefs about emotions. Psychological inflexibility partially mediated the relationship between internalized stigma and several patient outcomes (psychological distress, IBD health-related quality of life, IBD self-efficacy, and self-concealment) and completely mediated the relationship between internalized stigma and fatigue. CONCLUSION: Psychological inflexibility significantly impacts the quality of life in individuals with internalized stigma related to IBD and mediates the relationship between internalized stigma and patient outcomes. Increasing psychological flexibility in adults with IBD may reduce distress and enhance quality of life. Longitudinal studies and trials of psychological interventions targeting psychological flexibility warrant exploration.