Sedation management during extracorporeal membrane oxygenation(ECMO) is a common challenge encountered by treating intensivists. Data about the safety of propofol use during ECMO has been contradictory. We aimed to investigate associated risks of propofol use on oxygenator lifespan and to explore the effect of propofol use on oxygenator membranes when therapeutic anticoagulation was omitted. Adult respiratory ECMO patients who received propofol were retrospectively compared with those who did not, and outcomes were assessed by means of duration of oxygenator functionality before requiring an exchange, and number of exchanges during propofol use and/or ECMO support. Out of the 63patients included in the analysis, 46%received propofol during ECMO as part of sedation regimen. The use of propofol was not found to be associated with an increased incidence of oxygenator failure when compared with cohorts who did not receive propofol (21% propofol arm vs. 6% control, p = 0.13). When analyzed for anticoagulation omission effects, propofol did not increase the risk of oxygenator failure (p = 0.63). The only predictor that statistically predicted the risk of oxygenator failure was development of heparin-induced thrombocytopenia (HIT) during ECMO. The results of this study further support the previously reported safety of propofol utilization during respiratory ECMO even in the absence of anticoagulation.