BACKGROUND AND AIMS: Diffuse jejuno-ileitis of Crohn’s disease may be a homogeneous clinical subgroup. The aim of this work was to compare the demographic and clinical data at diagnosis and the initial treatments of patients with diffuse jejuno-ileitis of Crohn’s disease and to the ones without this localization. PATIENTS AND METHODS: For demographic and clinical studies, 48 (32M/16F) incident cases of diffuse jejuno-ileitis of Crohn’s disease diagnosed between 1988 and 1994 in the EPIMAD register were compared with 96 (48M/48F) controls diagnosed the same year. As far as for the therapeutic management, the 48 incident cases were compared with 48 controls. RESULTS: Diffuse jejuno-ileitis constituted 3.3% of the total incident cases. Median age at diagnosis was significantly lower (20 vs 23 years, P = 0.01) and an upper digestive involvement was more frequent (56% vs 34%, P = 0.03) in patients with diffuse jejuno-ileitis. These patients were more often treated by total parenteral nutrition (43.8% vs 19.6%, P = 0.01) or azathioprine (50% vs 20.8%, P = 0.005). Azathioprine was also introduced earlier (20.7 vs 40.3 months, P = 0.009). Surgery for resection was less often required in diffuse jejuno-ileitis than in controls (65.2% vs 99.8%, P = 0.02) while more stricturoplasties were performed (52.9% vs 10%, P = 0.003); overall surgical rates did not significantly differ in the 2 groups. CONCLUSION: Our series suggest that diffuse jejuno-ileitis of Crohn’s disease is a subgroup of patients characterized by a young age at diagnosis, with more frequent and earlier requirement for azathioprine.