BackgroundThis study was designed to evaluate the long‐term durability, oxygenation, and pressure loss of newly developed, methacryloyloxyethyl phosphorylcholine (MPC)‐polymer‐coated, nonporous silicone hollow fiber‐membrane lungs in vivo using a pulmonary artery‐to‐left‐atrium paracorporeal configuration.MethodsAn extracorporeal circuit from the pulmonary artery (device inflow) to the left atrium (device outflow) was established using dedicated composite vascular grafts in three healthy female goats for the prototype lung testing.ResultsDuration of testing the prototype lungs was 52, 57, or 100 days. Averages of oxygen transfer rates (ml/min) at the beginning of the evaluation were 77.6 ± 17.5 at 1 L/min blood flow, 137.1 ± 58.0 at 2 L/min, and 188.9 ± 86.4 at 3 L/min. Consistent oxygen transfer performance was maintained throughout the experiments. Electron microscopy revealed minimal thrombus formation on the hollow fiber membranes inside the lungs. Native lungs were maintained in good condition without appreciable congestion in all three subjects.ConclusionsThe longevity of the hollow fibers documented here is a key requirement for the development of a device for long‐term respiratory support. The pulmonary artery‐to‐left‐atrial configuration established with our composite vascular grafts could maintain long‐term functionality.