Background Despite significant advances in cardiac allograft preservation, the optimal preservative solution is unknown. We evaluated the impact of the most commonly used solutions in the USA, the University of Wisconsin solution (UW) and Celsior solution (CS), on outcomes after orthotopic heart transplantation (OHT). Methods We retrospectively reviewed adult OHT recipients in the United Network for Organ Sharing (UNOS) database. Primary stratification was by preservation solution. The primary end-point was short-term survival (30 days and 1 year). Secondary end-points included common post-operative complications. Subgroup analysis was performed in high-risk allografts (donor age >50 years or ischemic time >4 hours). Risk-adjusted multivariate Cox proportional hazard regression was used to assess survival. Results From 2004 to 2009, 4,910 patients (3,107 UW and 1,803 CS) with sufficient preservation solution information for analysis underwent OHT. Baseline characteristics were well-matched between the two groups. UW was associated with a small but significantly improved survival compared with CS at 30 days (96.7% vs 95.4%, p = 0.02) and 1 year (89.6% vs 87.0%, p < 0.01). These survival differences persisted on multivariate analysis at 30 days (HR 1.47 [1.02 to 2.13], p < 0.05) and 1 year (HR 1.40 [1.14 to 1.73], p < 0.01). In the 1,455 patients with high-risk allografts, preservation with UW was associated with improved survival compared with CS at 30 days (94.3% vs 91.3%, p < 0.01) and at 1 year (84.2% vs 80.19%, p < 0.01), a difference that was significant according to multivariate Cox analysis at 30 days (HR 2.29 [1.39 to 3.76], p < 0.01) and 1 year (HR 1.61 [1.17 to 2.21], p < 0.01). Conclusions Preservation with UW solution is associated with improved short-term survival compared with CS. Patients undergoing OHT with high-risk allografts have a similar survival benefit.