Background: The objective of this study was to investigate the effect of the perioperative use of methylprednisolone in medium doses on markers of endothelial cell activation in patients with coronary artery disease undergoing cardiopulmonary bypass. Methods: In this prospective, double-blinded, placebo-controlled, randomised study, 44 patients, undergoing a coronary artery bypass graft surgery received either methylprednisolone 20mg/kg or a placebo intraoperatively after anaesthesia induction. The primary endpoint was endothelin-1, and secondary endpoints were E-selectin, interleukin (IL)-6 and IL-10, PaO₂/FiO₂ coefficient, and microalbuminuria. Results: Endothelin-1 was higher in the study group postoperatively at 10min (p=0.0008), 2h (p=0.02), 4h (p=0.005), and 24h (p=0.004). IL-6 was lower in the study group postoperatively at 2h (p=0.03), 4h (p=0.04), and 24h (p<0.0001). IL-10 was higher in the study group postoperatively at 10min (p<0.0001), 2h (p=0.009), and 4h (p=0.001). PaO₂/FiO₂ was lower in the study group at 24h after surgery (p=0.03). Microalbuminuria was similar in both groups. Conclusion: Despite an obvious anti-inflammatory effect, methylprednisolone causes endothelial cell activation in patients undergoing cardiopulmonary bypass.