Primary graft failure has been broadly defined as cardiac and circulatory insufficiency in the immediate postoperative period after cardiac transplantation. Risk factors for primary graft failure have been identified in the donor, recipient, and within the perioperative period. Donor serum biomarkers have been identified. The use of donor serum cardiac troponin levels, while most studied, is of questionable value. Basic markers of renal and hepatic function in the recipient are associated with risk of hospital mortality after transplant. HLA antibodies in the recipient to donor HLA antigens are a marker of primary graft failure. Accumulating experience and investigation suggest that cardiac transplantation may be performed in the presence of low levels of donor specific antibodies. Increasing sophistication in the assessment of HLA antibodies may allow for a more precise assessment of their impact on allograft function and survival and increase the capability to transplant these sensitized children.