Extracorporeal life support (ECLS) is used to support patients with pulmonary alveolar proteinosis (PAP) both during acute illness and during lung lavage therapies. We report the challenges encountered while providing ECLS for respiratory failure to a 12-year-old girl with PAP who had previously received ECLS as a toddler for a prior episode of respiratory failure due to PAP. She was placed on venovenous-arterial (VVA) ECLS and subsequently switched to venovenous (VV) ECLS with drainage from the right femoral vein and reinfusion by a long cannula placed into the right atrium. Our case illustrates standard cannulation may not be possible for children requiring a second ECLS course and the importance of considering alternative modes of cannulation and ECLS support when conventional methods are not possible.