The objectives of this work were to portray the incidence of upper gastrointestinal bleeding in central Greece and to define subsets at higher risk of poor outcome or death. Two hundred and sixty-four cases were recorded. The incidence was 116 per 100,000 per year (95% CI: 102-130). Re-bleeding was noted in 7.9% of patients. The case fatality was 7.2% and population mortality 8 per 100,000 per year (95% CI: 4-12). Independently significant risk factors for re-bleeding were stigmata of bleeding at endoscopy (OR: 3.11; 95% CI: 1.06-9.13, P = 0.04), smoking (OR: 3.39; 95% CI: 1.08-10.62, P = 0.03), and the use of anti-coagulant drugs (OR: 2.64; 95% CI: 1.00-7.13, P = 0.05), while the independently significant risk factor for death was re-bleeding (OR: 5.74; 95% CI: 1.40-23.52, P = 0.03). We conclude that patients with stigmata of bleeding at endoscopy and on anti-coagulant therapy should be under close surveillance because of the higher risk of re-bleeding. Smoking also increases the risk of re-bleeding. Patients with re-bleeding episodes must be managed intensively because of the higher risk of death.