This prospective randomized study compares novel hyaluronan-based heparin-bonded circuits vs. uncoated controls across EuroSCORE patient risk strata including biomaterial evaluation. Over a two-year period, 90 patients undergoing coronary artery bypass grafting were prospectively randomized to one of the two perfusion protocols: Group 1 was treated with hyaluronan-based heparin-bonded preconnected circuits (Vision HFO-GBS (TM), Gish, CA, USA) and Group 2 with identical uncoated controls. Each group was composed of three subgroups (n = 15) with respect to preoperative evaluation of low (EuroSCORE 0-2), medium (3-5) and high (6+) risk patients. Blood samples were collected after induction (T1) and heparinization (T2), 15 min after cardiopulmonary bypass start (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6). In high-risk patients, platelet counts demonstrated significant preservation at T4, T5 and leukocyte counts were lower at T5 in hyaluronan group (P <= 0.05 vs. control). C3a (ng.ml(-1)) levels were significantly lower at T3 (0.2 +/- 0.04 vs. 0.31 +/- 0.05), T4 (0.25 +/- 0.04 vs. 0.51 +/- 0.05), T5 (0.38 +/- 0.04 vs. 0.56 +/- 0.05) and interleukin-6 (pg.ml(-1)) at T4 (91 +/- 18 vs. 124 +/- 20), T5 (110 +/- 20 vs. 220 +/- 25) in coated group vs. control (P <= 0.05). Protein desorption (microalbumin) on fibers (mg.mm(-3)) was less in hyaluronan vs. control groups (P <= 0.05). Hyaluronan coating reduced platelet adhesion and cell adsorption, and modulated inflammatory response in high-risk patients. (c) 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.