Background: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology for many critically ill patients. Unfortunately, ECMO has a >40% mortality rate, partly due to lack of established dosing guidelines. Dosing is different in this population due to drug interactions with the ECMO circuit. Drugs can be adsorbed by the ECMO circuit via hydrophobic and electrostatic interactions, thereby decreasing the amount of drug available to the patient. Micellar encapsulation of drugs may prevent adsorption. Methods: Two types of propofol were compared in an ECMO ex-vivo system: the clinical formulation of propofol and micelle-encapsulated propofol. The ECMO system consisted of a reservoir, pump, and oxygenator, as well as ports for drug administration and sample collection. The ECMO systems were dosed with either clinical or micellar propofol, and drug concentrations were measured over time using an optimized High Performance Liquid Chromatography (HPLC) assay. Each drug was measured in triplicate. % Recovery at each timepoint was calculated by comparing the concentration at a given timepoint with initial concentration at 1 minute. Data was reported as the mean percent recovery with 95% confidence intervals. Results: Adsorption of propofol was significantly reduced (P<0.01) in micellar propofol compared to clinical propofol at earlier time points where 40% of the drug was recovered in case of micellar propofol compared to only 24% in case of clinical propofol at 30-minute time point. Conclusion: Micellar encapsulation significantly reduced drug adsorption in the ECMO circuit. The clinical significance of this reduction is not clear. Additional studies to optimize micellar encapsulation and decrease adsorption are needed.