Background: Neonatal foals with isoerythrolysis (NI) often die, but the risk factors for death have not been identified. Objectives: To identify factors associated with outcome in foals with NI and to identify factors associated with death from liver failure or kernicterus in the same population.Animals: Seventy-two foals with NI examined at referral institutions. Methods: Retrospective case series. Information on signalment, clinical examination findings, laboratory testing, treatment, complications, outcome, and necropsy results were obtained.Results: The overall survival rate was 75% (54 of 72). Liver failure (n 5 7), kernicterus (n 5 6), and complications related to bacterial sepsis (n 5 3) were the 3 most common reasons for death or euthanasia. The number of transfusions with blood products was the factor most strongly associated with nonsurvival in a multivariate logistic regression model. The odds of liver failure developing in foals receiving a total volume of blood products ! 4.0 L were 19.5 (95% confidence intervals [CI]: 2.13-178) times higher than that of foals receiving a lower volume (P 5 .009). The odds of kernicterus developing in foals with a total bilirubin ! 27.0 mg/dL were 17.0 (95% CI: 1.77-165) times higher than that of foals with a lower total bilirubin (P 5 .014).Conclusions and Clinical Importance: Development of liver failure, kernicterus, and complications related to bacterial sepsis are the most common causes of death in foals with NI. Foals administered a large volume of blood products are at greater risk for developing liver failure.