BACKGROUND: Among patients successfully resuscitated after an out-of-hospital cardiac arrest (OHCA), 10% to 15% evolve toward brain death (BD), thus becoming potential organ donors. RESEARCH QUESTION: Is it possible to establish a score for early estimation of BD risk after OHCA? STUDY DESIGN AND METHODS: The BD after cardiac arrest (BDCA) score was developed from data available within 24 hours after OHCA from two OHCA trials: Cyclosporine in Cardiac Arrest Resuscitation and Erythropoietin After OHCA. The BDCA score was then validated in another large prospective multicenter data set. The main outcome was the occurrence of BD. Independent prognostic covariates for BD were identified using a binomial two-stage adaptive least absolute shrinkage and selection operator procedure. RESULTS: The development cohort included 569 patients alive 24 hours after OHCA, among whom 84 (14.8%) experienced BD. Independent predictors of BD used to build the BDCA score were being female (4 points), nonshockable rhythm (24 points), cardiac cause of OHCA (-6 points), neurological cause of OHCA (45 points), natremia at 24 hours (natremia in millimoles per liter minus 140 points), and vasoactive drug at admission (4 points) and at 24 hours (6 points). The area under the curve (AUC) of the BDCA score was 0.82 (95% CI, 0.77-0.86), and the discrimination value in the validation cohort (n = 487) was consistent (AUC, 0.81; 95% CI, 0.76-0.86). In the validation cohort, BD occurred in 4.0%, 20.4%, and 67.7% of patients with scores of \textless 20, 20 to 50, and \textgreater 50, respectively. INTERPRETATION: The BDCA score allows early detection of patients with a high probability of experiencing BD, which may help increase organ donation after OHCA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01595958, and ClinicalTrials.gov; No.: NCT00999583; URL: www.clinicaltrials.gov.