This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG) were assigned to receive either a methylprednisolone loading dose (1mg/kg) followed by continuous infusion (2mg/Kg/24 hours for 1 day) (low-dose regime) or a single dose of methylprednisolone (15 mg/kg) before cardiopulmonary bypass (high dose regime). Serum concentrations of IL-6 and C- reactive protein (CRP) were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively). Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.