Heparin was covalently bonded to a new hollow-fiber dense membrane artificial lung and extracorporeal circuit using a silane coupling agent and polyethyleneimine. This study investigated whether prolonged, venoarterial bypass extracorporeal lung assist (V-A bypass ECLA) could be sustained in a goat by the combination of the new membrane lung and minimal systemic heparinization. We maintained ECLA with the hollow-fiber lungs (surface area, 0.8 m2) and circuits by titrating the activated clotting time (ACT) to below 150 s with minimal systemic heparinization in 5 goats. The outcome was assessed from the function of the artificial lung via macro and microscopic examinations after the experiments and the incidence of systemic complications. The 5 goats were maintained on ECLA for 6 to 27 days. The bypass flow rate, blood gases at the return and drainage sites, platelet counts, and platelet aggregation activity were well maintained. Although the hemoglobin concentration, hematocrit, and plasma protein at the start of the ECLA were significantly lower than the pre-ECLA values due to hemodilution, the values remained stable during ECLA. A cerebral infarction occurred in 1 goat. However, in the other 4 goats, no complications such as bleeding, thrombosis, or plasma leakage from the artificial lung were observed. Although several thrombi were observed in the stagnant area of the artificial lung, these local thrombi did not cause the function of the artificial lung to deteriorate. We found that this new type of highly biocompatible, dense membrane artificial lung, when combined with minimal systemic heparinization, prolonged ECLA without the deterioration of the artificial lung function and was suitable for prolonged ECLA.