Background: Several coating techniques for extracorporeal circulation have been developed to diminish the systemic inflammatory response during cardiopulmonary bypass (CPB). The aim of this study was to evaluate the clinical effectiveness and biocompatibility of heparin-coated and poly-2-methoxyethylacrylate (PMEA)-coated CPB circuits on coronary patients with left ventricular systolic dysfunction. Methods: Thirty-six patients who underwent elective coronary artery bypass grafting were divided into two equal groups: group H (n = 18), heparin-coated; group P (n = 18), PMEA coated. Clinical outcomes, hematologic variables, cardiac enzymes, malondialdehyde (MDA), and acute phase inflammatory response (including myeloperoxidase (MPO), catalase, hsCRP, and IL-8) were analyzed perioperatively. Results: Demographic, CPB, and clinical outcome data were similar for both groups. Plasma fibrinogen, total protein, albumin, and platelet count decreased, neutrophil count, MDA, IL-8, MPO, and catalase levels increased during CPB. During CPB, MPO and catalase values were significantly higher in group P (p = 0.02 and p = 0.01) and postoperative MDA concentration was lower in group H (p = 0.03). Platelet counts were better preserved in group H during and after CPB but neutrophil count and IL-8 level did not differ between the groups. Postoperative total protein, albumin, and fibrinogen levels were higher in group H (p < 0.05). The postoperative first day levels of troponin-I, CK-MB, and CRP increased in both groups without any significant differences between the groups. Conclusions: Heparin-coated circuit provided better suppression of perioperative inflammatory markers and exhibited more favorable effects on hematologic variables than PMEA-coated circuit.