Objective: To evaluate the feasibility of a closed-loop system for simultaneous control of systemic arterial and pulmonary artery blood pressures during cardiac surgery. Design: Feasibility study. Setting: The cardiac surgery operating room. Patients: The performance of the multiple-drug closed-loop system was evaluated during cardiac surgery in 30 patients who required treatment with more than one vasoactive or inotropic drug. Interventions: A multiple-drug closed-loop system integrated five single-drug blood pressure controllers. Arterial hypertension was controlled using sodium nitroprusside or nitroglycerin, arterial hypotension was controlled using noradrenaline or dobutamine, and pulmonary hypertension was controlled using nitroglycerin. The anesthesiologist selected target pressures and single-drug blood pressure controllers. The multiple-drug closed-loop system had a set of priority rules that automatically activated from the selected single-drug controllers the optimum single-drug controller for each hemodynamic state. Drug infusion rates of the nonactive controllers were kept constant. The initial knowledge that was used to construct the priority rules was obtained from standard anesthetic protocols on perioperative management of cardiac surgical patients. A supervisory computer program defined the actions to be taken in cases of infusion pump problems, invalid pressure measurements, and during unexpected increases and decreases in systemic arterial pressure. Measurements and Main Results: The activation of single-drug controllers by the priority rules was accurate and fast. On average, a different single-drug controller was activated once every 7.2 mins. As a measure of variability, the average deviation of mean arterial pressure and mean pulmonary artery pressure from their target values was evaluated and was 8.6 +/- 4.0 and 4.4 +/- 4.0 mm Hg, respectively, before cardiopulmonary bypass and 8.0 +/- 3.6 and 2.4 +/- 0.9 mm Hg, respectively, after cardiopulmonary bypass. None of the single-drug controllers showed any signs of unstable response.