Over the last 8 years, we have developed and evaluated a continuous-flow total artificial heart (CFTAH) comprising two rotary blood pumps. To understand the physiologic effects of nonpulsatile circulation, we evaluated the CFTAH in 65 calves for 90 days or less. We describe our experience with 29 calves that survived for 7 days or more. The calves received dual axial-flow (n = 24) or centrifugal-flow (n = 5) pumps. Several iterations of customized atrial cuffs were developed to facilitate an adequate anatomical fit. Pressures (arterial pressure [AoP], pulmonary artery pressure [PAP], left atrial pressure [LAP], and right atrial pressure [RAP]) and pump parameters were continuously monitored. Hematologic and biochemistry values were analyzed. After each case, a necropsy was performed. The calves survived for 7–92 days (mean, 24 days). Pressures were 94 ± 14 (AoP), 25 ± 8 (PAP), 14 ± 6 (RAP), and 16 ± 6 (LAP) mm Hg. Pump flow was maintained at 9.1 ± 1.7 L/minute (right) and 9.4 ± 1.9 L/minute (left). Hematologic and biochemistry values remained acceptable. Eight animals underwent treadmill evaluations, in which oxygen consumption (VO2) was comparable with physiologic total-body VO2. In the two animals that survived to 90 days, the end-organs appeared unremarkable at autopsy, and the CFTAH circuits were free of thrombus. Our results show that a CFTAH can maintain a large animal physiologically and hemodynamically for up to 90 days with continuous flow.