BACKGROUND & AIMS: With increasing incidence, late-onset UC represents an important issue for the near future, but its outcome and relative therapeutic strategies are yet poorly addressed. This study has been undertaken to better define the natural history of late-onset ulcerative colitis. METHODS: In a multicenter retrospective study, disease presentation and course in the first 3 years after diagnosis were investigated in 1,091 UC patients divided into three age groups (diagnosis ≥65 years, 40-64 years, and <40 years). Disease patterns, medical and surgical therapy and relative risk factors for outcomes were analyzed. RESULTS: Chronic active or relapsing disease accounts for 44% of patients with late onset UC. In all groups, these disease patterns require 3 to 7-fold more steroids than remitting disease, but immunomodulators and, to a lesser extent, biologics are less frequently prescribed to the elderly. Advanced age, concomitant diseases and related therapies were found to be inversely associated with the use of immunomodulators or biologics, but not with surgery. CONCLUSIONS: Disease onset followed by a mild course was more frequent in patients diagnosed with UC ≥65 years, but a generalized assumption that late-onset UC follows a mild course may apply only to a subset of patients. A sizeable number of elderly patients present with more aggressive disease. Since steroid use and surgery rates did not differ in this subgroup, lower use of immunosuppressive therapy and biologics may reflect concerns in prescribing such therapies in the elderly.