Background: Exposure-based cognitive-behavioral therapy (exposure-CBT) is efficacious for irritable bowel syndrome (IBS). However, few patients receive exposure-CBT due to a lack of behavioral health providers trained in brain-gut behavior therapies.Nurse practitioners (NPs) could fill a critical need for scalable delivery methods. In a pragmatic investigation of a 5-session NP-delivered exposure-CBT for adults with Rome IV-defined IBS, we evaluated treatment feasibility and acceptability and explored changes clinical outcomes.Methods: Exposure-CBT was delivered as part of routine care involving four sessions every other week and a 2-month booster session. Patients could electively participate in an observational study including pre-, mid-, and post-treatment surveys and a post-treatment qualitative interview. Independently coded ratings of NP treatment protocol adherence and competence ratings were completed from audio recordings, rated on a 1 (not at all) to 5 (completely) scale.Results: Twenty-five patients consented (ages 22-67 years; 76% female; 48% IBSdiarrhea predominant). There was high feasibility-adherence average = 4.1, NP competence average = 4.8, 72% treatment completion, 93% satisfaction scores ≥3.Treatment satisfaction was high (rated as 4/4 "very satisfied" by n = 9 and as 3/4 "mostly satisfied" by n = 5). There were improvements in clinical outcomes across treatment with large effects for IBS-symptom severity (−53%; Hedge's g = 1.0; 95% confidence interval [CI] = 0.5, 1.5) and IBS quality of life (+31%; Hedge's g = 0.8; 95% CI = 0.4, 1.2).Conclusions: NP-delivered exposure-CBT for IBS was initially feasible and acceptable with promising clinical improvements. Findings will inform a future NIH Stage 1B/ ORBIT Phase IIB pilot randomized control trial.