The Oximetrix III Opticath (Abbott Critical Care Systems) is used for continuous measurement of venous saturation in a variety of applications, including extracorporeal membrane oxygenation (ECMO), despite clinical reports that have presented data showing poor accuracy of these devices. The CDI Blood Parameter Monitoring System 500 (Terumo) is an inline blood gas monitoring tool commonly used during cardiopulmonary bypass procedures to continuously assess oxygen saturation, blood gases, potassium, and bicarbonate. The purpose of this experiment was to compare the Opticath and the CDI 500 in trending venous blood saturation during a simulation of ECMO. An ECMO simulation circuit consisting of a silicone rubber membrane oxygenator and a stainless steel heat exchanger was constructed, and a standard venous reservoir bag was used to represent the patient. The CDI and the Opticath were incorporated side by side into a shunt that originated just before the oxygenator and returned flow to the venous line. The circuit was primed with fresh porcine blood and conditioned with the addition of CO2 to simulate typical venous blood under ECMO conditions. After an initial calibration procedure, samples were drawn and analyzed by an AVL Opti CCA (Roche/Osmetech) every 4–8 hours for a period of 7 days, with calibration of each device at sample intervals. The data were plotted, and a least squares regression line was calculated. The average error for venous saturation of the CDI and Opticath after 72 hours was 3.86 and 9.51 respectively. At 168 hours, error for the CDI was 8.37, and the Opticath had an error of 14.78. A correlation analysis of the CDI and AVL CCA analyzer yielded a correlation coefficient of r = .88 at 72 hours and r = .84 at 168 hours. Correlation between the Opticath and the AVL CCA yielded a correlation coefficient of r = .77 at 72 hours and r = .55 at 168 hours. Based on these findings, the CDI 500 is an effective tool for monitoring venous blood saturation under simulated conditions of ECMO.