Autoimmune enteropathy (AIE) is a rare autoimmune disorder that has been described both in pediatric and adult patients and usually causes intractable watery diarrhea. The management of AIE is not standardized because the disease shows variable response to different immunosuppressive regimens including corticosteroids, azathioprine, cyclophosphamide, 6-mercaptopurine, tacrolimus, cyclosporine-A, infliximab, vedolizumab, and abatacept. We present a patient with adult-onset AIE and intractable high-volume diarrhea resulting in numerous hospitalizations and temporary parenteral nutrition, who is now successfully maintained on ustekinumab. Therefore, ustekinumab should be considered for further evaluation as a therapeutic option in cases of refractory AIE.