We have developed a low negative pressure vacuum suction system in which cardiotomy suction is performed by the negative pressure of the venous reservoir controlled by a vacuum controller. We have employed this vacuum suction system with a centrifugal pump as a totally roller pumpless cardiopulmonary bypass (CPB) system. In this study, the clinical availability and hemocompatibility of our totally roller pumpless CPB system were evaluated by a randomized prospective study. Thirty patients undergoing aortocoronary bypass grafting were assigned to the study. Data from seventeen patients treated with a totally roller pumpless CPB system were compared with data from 13 treated with a conventional roller pump CPB system. Totally roller pumpless CPB reduces hemolysis, showing lower plasma free hemoglobin levels (81.8 ± 25.0 versus 42.0 ± 16.3 at 30 min after CPB initiation, p < 0.05). higher plasma haptoglobin levels (37.8 ± 36.6 versus 77.2 ± 31.3 at 120 min after CPB, p < 0.05), and lower blood lactate dehydrogenase (LDH) levels (1391 ± 497 versus 972 ± 187, p < 0.01) than those of CPB with a roller pump suction with no significant difference between platelet counts. Arterial blood oxygen tension after using a totally roller pumpless CPB system was slightly better than that with a roller pump (396 ± 48 versus 437 ± 43, p = 0.069): however, there was no significant difference in intubation times between groups. A totally roller pumpless CPB system provides sufficient biocompatibility for the blood to reduce hemolysis significantly and simplifies and rniniaturizes the entire CPB system to achieve good visuality and handling for control as well.