Because acute systemic hypertension early after cardiac surgery has been linked to catecholamine elevation, an open-label, randomized, crossover study was performed to compare the efficacy of esmolol, a new ultra-short-acting intravenous β-blocking agent, to nitroprusside, the standard therapy. Controlled drug infusions to maximal dosage (esmolol, 300 μg/kg/min, and nltroprusside, 10 μg/kg/min) were titrated to achieve at least a 15% reduction in systolic pressure. The blood pressure (BP) endpoint was achieved with esmolol (within 29 ± 14 minutes) in 18 of 20 patients (90%), compared with 19 of 20 (95%) with nitroprusside infusion (within 21 ± 15 minutes, difference not significant [NS]). Systolic BP decreased from 170 ± 13 to 136 ± 12 mm Hg (mean ± standard deviation) with esmolol and from 170 ± 13 to 141 ± 13 mm Hg with nitr roprusside infusion (both p <0.05). Diastolic BP was reduced from 71 ± 12 to 64 ± 11 mm Hg with esmolol and from 71 ± 12 to 52 ± 13 mm Hg with nitroprusside infusion (both p <0.05). Esmolol infusion resulted in decreased heart rate, cardiac index and stroke volume index and Increased right atrial pressure (all p <0.05), whereas nitroprusside infusion resulted in increased heart rate and cardiac index and decreased right atrial pressure, pulmonary arterial wedge pressure and systemic vascular resistance (p <0,05). Esmolol therapy did not significantly change arterial PaO 2 (138 ± 40 vs 137 ± 43 mm Hg) or oxygen saturation (98 ± 1 vs 99 ± 1 vol %), whereas nitroprusside reduced both (from 124 ± 31 to 72 ± 13 mm Hg and 98 ± 1 to 94 ± 3 vol % , respectively, p <0.05). Esmolol therapy markedly Increased pulmonary arterial wedge pressure in 1 patient with severe left ventricular dysfunction. Diastolic blood pressure decreased to less than 50 mm Hg in 1 patient during esmolol and in 11 patients during nitroprusside therapy. Thus, both drugs result in rapid and titratable control of BP, esmolol by β-blockade and nitroprusside through vasodilator effects. Esmolol has the advantage of resulting in no adverse effects on arterial oxygen saturation, but should be avoided If the patient has severe ventricular dysfunction.