In March 2004, the National Heart, Lung, and Blood Institute awarded five contracts to develop devices providing circulatory support for infants and small children with congenital and acquired cardiac disease. Since 2004, the team at Penn State College of Medicine has developed a pneumatically actuated ventricular assist device (VAD) with mechanical tilting disk valves. To date, hemodynamic performance, thrombogenesis, and hemolysis have been chronically evaluated in 16 animals, including 4 pygmy goats and 12 sheep. Major complications, mainly respiratory failure, have been encountered and resolved by a multi-disciplinary team. Multi-modal analgesia, appropriate antibiotic therapy, and attentive animal care have contributed to successful outcomes. Time after implant has ranged from 0 to 40 days. Most recently, a sheep implanted with Version 3 Infant VAD was electively terminated at 35 days postimplant, with no major adverse events. This report describes a successful in vivo model for evaluating a pediatric VAD.