Early cardiac graft failure has been reported to occur in 4-25% of patients undergoing orthotopic heart transplantation. To further elucidate the characteristics and prognosis of patients with graft failure, we retrospectively identified 10 patients from a series of 212 consecutive recipients with catastrophic graft dysfunction in the absence of acute cellular rejection, right ventricular failure secondary to pulmonary hypertension and technical factors. We present a case report and the experience from one transplant center, a review of the literature and possible strategies for the management of early graft failure. Mean onset of graft failure was 6.5 days (range intraoperative to 23 days). Multivariable analysis revealed a longer total ischemic time in patients with early graft dysfunction (200 +/- 14 vs. 166 +/- 4 min). No episodes of hyperacute rejection were observed. Pathologic changes noted on biopsy or autopsy included ischemia in 9 and vascular rejection in 1. The mortality at 60 days was 50%. Early use of aggressive mechanical and pharmacological support is described and appears to be important for graft salvage.