Objectives: To identify the remifentanil dosing regimen providing safe and optimal anesthetic conditions during coronary artery bypass graft surgery and to evaluate postoperative recovery characteristics. Design: Open-label, randomized, parallel group. Setting: Three centers in the United States. Participants: Seventy-two patients with left ventricular stroke volumes greater than or equal to50 mL. Interventions: Patients were randomized to remifentanil doses of 1 mug/kg/min (group 1, n = 23); 2 mug/kg/min (group 2, n = 24), or 3 mug/kg/min (group 3, n = 25). Somatic, sympathetic, and hemodynamic responses indicating inadequate anesthesia were treated with bolus doses of remifentanil, 1 to 2 mug/kg, and infusion rate increases, and, if necessary, isoflurane 0.5% to 1.0% was added as a rescue anesthetic. In the intensive care unit, the remifentanil infusion was reset to 1 mug/kg/min, with midazolam administered for supplemental sedation and morphine for analgesia. Measurements and Main Results: The durations of anesthesia, surgery, and cardiopulmonary bypass were similar for the 3 study groups. In addition, dose of lorazepam premedication, time to loss of consciousness, preoperative left ventricular ejection fraction, age, weight, and sex were similar for the 3 study groups. Remifentanil alone (infusion and boluses) prevented and controlled all responses to stimulation in 44% of group 3, 37% of group 2 and 9% of group 1 patients intraoperatively. Isoflurane (0.5%-1% inspired) rescue was successful in the remaining patients in each group. Hypotension indicating discontinuation of isoflurane and reductions of remifentanil infusion rates occurred in 64% to 75% of all patients. The optimal range of remifentanil infusion was 2 to 4 mug/kg/min with isoflurane to supplement the opioid. Fifty-one patients (71%) met the criteria for extubation within 6 hours postoperatively; because of surgical practice differences, only 30 patients (59%) were actually extubated. Conclusions: After lorazepam premedication, remifentanil infusion (2-4 mug/kg/min) supplemented intermittently with low inspired concentrations of isoflurane provided an effective anesthetic regimen for coronary artery bypass graft surgery. Early extubation times were feasible after remifentanil continuous infusions (1-5 mug/kg/min) used as the primary anesthetic component intraoperatively and for analgesia (less than or equal to1 mug/kg/min) in the immediate postoperative setting. Copyright 2003, Elsevier Science (USA). All rights reserved.