A novel cardiopulmonary support (CPS) system as a long-term total substitute for the natural heart and lung was designed and evaluated. The CPS system is composed of a ventricular assist device (VAD) and a newly developed compact artificial lung (AL). The pneumatic VAD was originally developed in the authors' institute and has proven durable and antithrombogenic in over 120 clinical uses. The AL, with 1.2 m2 membrane surface area and 140 ml priming volume, consists of a special gas exchange membrane where not only are micropores blind-ended to prevent serum leakage, but the blood contacting surface is treated with heparin binding to ease systemic anticoagulation. Chronic animal experiments of total CPS were carried out in three goats weighing from 28 to 36 kg. Venoarterial bypass was instituted with the CPS system in which all venous blood was drawn from both the right atrium and ventricle and returned to the aorta. No systemic anticoagulation was conducted except for heparin added fluid infusion from pressure lines. One animal survived for 2 weeks without any device related problems until electively euthanized. Blood flow rate ranged between 3.2 to 4.5 L/min, O2 transfer between 120 to 220 ml/min, and CO2 removal between 60 to 210 ml/min. No substantial changes were found in platelet count or other coagulation factors. These results indicate that the system has the ability to be used for long-term CPS, such as a bridge to lung or heart-lung transplantation.