A new generation of coating extracorporeal circuitry with biocompatible polymers has entered the North American perfusion market. This new biomimetic coating process uses synthetic phosphorylcholine (PC) containing polymers to bond covalently to the surface of the Sorin Monolyth oxygenator, under the brand name of Mimesys. In part one of a three-part investigation, 160 Mimesys-coated oxygenators were randomly evaluated against 36 uncoated oxygenators for blood flow, hemodynamic resistance, and pressure differentials. In part two, retrospective analysis of platelet data collected in this study was compared with platelet data collected from a previous investigation using uncoated Monolyth oxygenators with albumin and crystalloid perfusates. Part three examined the risk-adjusted clinical outcomes of 71 patients treated with Mimesys-coated oxygenators, compared with 71 case-matched patients treated with uncoated oxygenators. There was no difference found in the Mimesys-coated group, when compared to the control group, with regard to pressure differentials or hemodynamic resistance. However, we conclude that platelet protection with PC-coated Monolyth's using crystalloid perfusates, was similar to platelet protection with albumin perfusates, and significantly better than uncoated Monolyths using crystalloid perfusates.