BACKGROUND: Collagenous sprue (CS) is a rare form of enteropathy that had been reported to be associated with celiac disease (CD) and collagenous colitis (CC). The aim of our study was to compare the clinical features, treatments, and outcomes of CS, CD, and CC. METHODS: All patients with histologic diagnosis of CS, CD, or CC with complete clinical data were extracted from our pathology database between 1990 and 2015. Demographic and clinical features were recorded along with treatments and outcomes. RESULTS: A total of 21 patients with CS were included. Overall CS patients were more symptomatic with 17 (81.0%) patients with diarrhea and 15 (71.4%) with unintentional weight loss. Positive celiac serology was noted in 5 (23.8%) CS patients. CS patients had higher rates for disease-related temporary total parenteral nutrition (TPN) use (38.1% vs. 1.1% vs. 1.0%, P < 0.0001) and disease-related hospitalization (52.4% vs. 3.3% vs. 8.2%, P < 0.0001) than that in CD and CC patients. Twenty CS patients received treatments, including the combination of gluten-free diet (GFD) and corticosteroids (n = 12), GFD only (n = 2), and corticosteroids only (n = 6). All CS patients showed symptomatic reliefs with treatment. Although CS patients had a higher rate for hospitalization and TPN use, disease-related death was not observed in all three groups. CONCLUSIONS: Collagenous sprue patients had more severe clinical presentation than patients with CD and CC and therefore had higher demand for temporary TPN and hospitalization. Nevertheless, a prompt use of steroids and/or GFD upon histologic diagnosis of CS may have contributed to an overall excellent prognosis.