Objective This study aimed to compare the efficacy of losartan, an angiotensin II receptor antagonist, with propranolol on portal hypertension in patients with decompensated chronic liver disease. Methods In all, 30 patients with ChildPugh B cirrhosis and large varices without any prior therapy for portal hypertension were randomized to either losartan (n=15) or propranolol (n=15). Clinical, biochemical and hemodynamic parameters including hepatic venous pressure gradient (HVPG), wedged hepatic venous pressure (WHVP), mean arterial blood pressure (MABP) and free hepatic venous pressure (FHVP) were measured at baseline and after 4-week therapy. Patients with HVPG<12mmHg were regarded as responders. Results An equal number of responders were seen in both groups (6/15, 40.0%). The reduction of WHVP and HVPG was greater in the losartan group than in the propranolol group, although no significant differences between them were found. Heart rate decreased more in the propranolol arm than in the losartan arm (P<0.01); however, no correlation between the decrease of heart rate and the reduction of HVPG was observed. One patient in the losartan group, although a responder, had gastrointestinal bleeding 2 months after the drug administration, but the varices were small under endoscopy and did not require definitive therapy. The fall of MABP was greater with losartan, with no statistical difference between the two groups. Conclusion The effect of losartan was comparable to propranolol in reducing portal pressure in decompensated ChildPugh B chronic liver disease.