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Membrane oxygenator exchange can be a frequent requirement during extracorporeal membrane oxygenation (ECMO). In low-income health systems, the scarcity and cost of disposables pose significant challenges to timely exchanges. We describe a 48-year-old woman placed on veno-venous ECMO for refractory hypoxemic respiratory failure secondary to pneumonia. Within 30 min, the oxygenator developed thrombosis, characterized by a transmembrane pressure gradient of 229 mmHg. A total of 10 mg of recombinant tissue plasminogen activator (rt-PA) was administered through the premembrane port. Sixty minutes after infusion, the gradient decreased to 116 mmHg, with subsequent improvement in oxygenation. No bleeding occurred. The patient was successfully weaned from ECMO and discharged from the ICU without complications. Low-dose rtPA instillation into a failing oxygenator can postpone exchange and represents a viable salvage strategy for resource-limited ECMO programs.