Only some patients show a substantial hepatic venous pressure gradient (HVPG) reduction after propranolol, which makes it desirable to investigate drugs with greater portal hypotensive effect. The aim of this study was to investigate whether carvedilol, a nonselective beta-blocker with anti-alpha1 –adrenergic activity, may cause a greater HVPG reduction than propranolol. Thirty-five cirrhotic patients had hemodynamic measurements before and after the random administration of carvedilol (n = 14), propranolol (n = 14), or placebo (n = 7). Carvedilol markedly reduced HVPG, from 19.5 ± 1.3 to 15.4 ± 1 mm Hg (P < .0001). This HVPG reduction was greater than after propranolol (−20.4 ± 2 vs. −12.7 ± 2%, P < .05). Moreover, carvedilol decreased HVPG greater than 20% of baseline values or to ≤12 mm Hg in a greater proportion of patients (64% vs. 14%, P < .05). Both drugs caused similar reductions in hepatic and azygos blood flows, suggesting that the greater HVPG decrease by carvedilol was because of reduced hepatic and portocollateral resistance. Propranolol caused greater reductions in heart rate and cardiac output than carvedilol, whereas carvedilol caused a greater decrease in mean arterial pressure (−23.1 vs. −11%, P < .05). Thus, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis, suggesting a greater therapeutic potential. However, it causes arterial hypotension, which calls for careful evaluation before its long-term use