Background No consensus exists on the optimal heart preservative solution (HPS) for cardiac allograft preservation. The significance of varying degrees of acute ischemic necrosis (AIN) in early transplant biopsy specimens is unknown. We investigated the effects of HPS on early cardiac histopathology by developing a novel grading system of AIN. Methods A retrospective review of our institutional database of orthotopic heart transplants (OHT) identified hearts preserved with University of Wisconsin (UW) or Celsior solutions. AIN severity was graded on early post-transplant biopsy specimens. Primary stratification was by HPS. Multivariable models examined mortality, AIN grade, primary graft dysfunction (PGD), and right heart failure (RHF). Results From 1996 to 2010, 42 of 174 adult OHTs were preserved with UW and 132 with Celsior, from which 431 biopsy specimens were reviewed. UW and Celsior had similar 30-day (p = 0.79) and 1-year mortality (p = 0.92). Celsior was associated with significantly more AIN on the first (p = 0.02) and second (p = 0.04) specimens and persisted on multivariable analysis for the first (odds ratio, 2.93; 95% confidence interval, 1.26–6.83; p = 0.01) and second biopsy specimen (2.08; 0.99–4.34; p = 0.05). When stratified by AIN score, 30-day and 1-year mortality were similar (p > 0.05). Adjusted analysis showed increasing AIN score on the first biopsy was strongly associated with an increased incidence of PGD (1.59; 1.02–2.47; p = 0.04) and RHF (2.45; 1.14–5.27; p = 0.02). Conclusions Our grading system provides a simple, reproducible method for determining AIN. UW is associated with less AIN than Celsior solution. Early biopsy ischemia is associated with PGD and RHF. AIN may have prognostic significance and its routine evaluation should be considered.