Early graft failure (EGF) is a dreaded complication after heart transplantation (HT). Despite several improvements, no effective therapy has been developed and the prognosis is poor. We evaluated the risk factors and clinical impact of EGF. In a consecutive series of 317 HTs performed at a single institution between January 1999 and December 2008, variables associated significantly with EGF were sought in bivariate and multivariable discriminant analyses. The deriving propensity score was used to stratify the study sample in to three groups (low, intermediate and high risk for EGF). Comparisons were performed between the higher-risk group and the remaining population in terms of preoperative features and outcomes. EGF occurred in 10.1% of the overall population (2.9, 3.8 and 23.6%, respectively, in the three groups). Overall, EGF-related mortality was 56.3% (100, 75 and 48%, respectively, in the three groups). Determinants of EGF in the highest-risk group were: redo procedure, valvular cardiomyopathy, status one at transplant, recipient male sex, donor-recipient (D/R) weight mismatch, high inotropic donor support, ischaemic time and first day troponin I release. In conclusion, several donor and recipient features predicted EGF. Since such characteristics are not readily modifiable but synergistically determine the occurrence of EGF, optimization of D/R matching is crucial to prevent it.