Whether an anticoagulation strategy combining bivalirudin and aspirin during extracorporeal membrane oxygenation (ECMO) would prolong oxygenator use is unknown. No clear data exist on oxygenator life span during prolonged ECMO use. We evaluated 70 adult patients who received ECMO due to coronavirus disease 2019 (COVID-19)–associated acute respiratory distress syndrome for at least 7 days and who required no or at least one ECMO oxygenator replacement due to ECMO-circuit thrombosis. Anticoagulation parameters mainly included activated partial thromboplastin time (aPTT), with monitoring of international normalized ratio and platelet count. The main target aPTT was 45–60 seconds. The indication for oxygenator replacement was ECMO-circuit thrombosis. The mean ECMO duration was 41.8 ± 25.3 days. No oxygenator replacement was required in 48 patients (68.6%) during a mean of 34.9 ± 23.5 ECMO days (range 7–104). Twenty-two patients (31.4%) required 35 oxygenator replacements throughout a mean ECMO duration of 56.9 ± 22.8 days (range 19–102). The mean aPTT was similar throughout ECMO in the two groups. A higher percentage of out-of-target aPTT was associated with a shorter duration of oxygenator use. Bivalirudin plus aspirin may prove to be a more appropriate anticoagulation strategy during ECMO, resulting in more effective utilization of ECMO oxygenators.