Laboratory testing is a helpful tool for clinicians, but can be costly and harmful to patients. A quality improvement project was initiated to reduce laboratory testing for patients receiving extracorporeal membrane oxygenation (ECMO) in a pediatric intensive care unit (PICU) at a tertiary care center. Preliminary data was gathered to demonstrate preimplementation practice, cost, and patient need for packed red blood cell (pRBC) transfusions. A new protocol was created by an interprofessional team based on best practice and benchmarking with high-performing organizations. The project was evaluated using two comparison groups, pre- and postimplementation for anyone receiving ECMO therapy in the PICU. The average laboratory tests per ECMO day decreased by 52% (128.4 vs. 61.1), cost per case decreased by 14.7%, pRBC transfusions decreased from 100% to 85%, length of stay (LOS) decreased by 8 days, and mortality rates decreased by 9.5%. The revised pediatric ECMO laboratory testing guidelines were successfully implemented and reduced laboratory cost without adverse effects on mortality rates or LOS.