To compare the efficacy of oral propranolol and sclerotherapy in the prevention of first hemorrhage from esophageal varices, 65 cirrhotic patients with moderate to large esophageal varices and no history of bleeding were included in the prospective controlled trial. After randomization, 33 patients received propranolol at a does reducing the heart rate by 25%; 32 patients were treated with intra-variceal and extra-variceal injection of ethanolamine oleate. On entry to the trial, the two groups were comparable in terms of clinical and biological parameters. The patients were observed for up to 60 months, with an average of 31 months. Nine patients bled (5 in propranolol and 4 in sclerotherapy) during follow-up. No significant difference were observed between propranolol and sclerotherapy in the cumulative bleeding rate and survival. The multivariate Cox model indicated that drug compliance in the propranolol group and high portal pressure in the sclerotherapy group were factors predictive of the first hemorrhage. These data support that propranolol and sclerotherapy are of comparable value in preventing the first hemorrhage in cirrhotic patients with esophageal varices.