The purpose of this study was to assess the clinical, epidemiological, therapeutic and prognostic changes observed in patients with upper gastrointestinal bleeding (UGIB) during the last two decades. Two cohorts of 200 patients with UGIB consecutively recruited during the period 1984-1987 (cohort A) then during the period 2004-2006 (cohort B) were compared. Median age was 61.5 years in the cohort A and 67 years in the cohort B. The main etiologies remained variceal bleeding and peptic ulcer, but esophagitis and Mallory-Weiss syndrome were more frequently observed recently. The intake of gastrotoxic drugs did not decreased despite the widely acknowledged harmful effects of these drugs. Regarding management practices, a therapeutic intervention during the first endoscopy was performed in 36% of the cases in the cohort B but only in 2% of the cases 20 years ago. The frequency and the volume of blood transfusion dramatically decreased during the last two decades. Regarding the outcome, the requirement for surgery and the rate of recurrent bleeding decreased by half, but mortality remained unchanged. The main changes observed in patients admitted for UGIB 20 years apart concerned epidemiological features, treatment and prognosis.