The number of patients who require orthotopic heart transplantation (OHT) for failing Fontan physiology continues to grow; however, the methods and tools to evaluate risk of OHT are limited. This study aimed to identify a set of preoperative variables and characteristics that were associated with a greater risk of postoperative mortality in patients who received OHT for failing Fontan physiology. Thirty-six Fontan patients were identified as having undergone OHT at University of California-Los Angeles Medical Center from 1991 to 2014. Data were collected retrospectively and analyzed. The primary end point was designated as postoperative mortality. After an average follow-up time of 3.5 years, 17 (44%) patients suffered postoperative mortality. Patient characteristics including (1) age <18 years at the time of OHT, (2) Fontan-OHT interval of <10 years, (3) systemic ventricular ejection fraction <20%, (4) moderate-to-severe atrioventricular valve insufficiency, (5) an elevated Model of End-stage Liver Disease, eXcluding INR score, or (6) need for advanced mechanical support before surgery were associated with an increased incidence of postoperative mortality. Using these risk factors, we present a theoretical framework to stratify risk of postoperative death in failing Fontan patients after OHT. In conclusion, a method such as this may aid in the transplantation evaluation and listing process of patients with failing Fontan physiology.