In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump.