OBJECTIVES: Visual assessment of the electroencephalogram by experienced clinical neurophysiologists allows reliable outcome prediction of approximately half of all comatose patients after cardiac arrest. Deep neural networks hold promise to achieve similar or even better performance, being more objective and consistent. DESIGN: Prospective cohort study. SETTING: Medical ICU of five teaching hospitals in the Netherlands. PATIENTS: Eight-hundred ninety-five consecutive comatose patients after cardiac arrest.None. MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalogram was recorded during the first 3 days after cardiac arrest. Functional outcome at 6 months was classified as good (Cerebral Performance Category 1-2) or poor (Cerebral Performance Category 3-5). We trained a convolutional neural network, with a VGG architecture (introduced by the Oxford Visual Geometry Group), to predict neurologic outcome at 12 and 24 hours after cardiac arrest using electroencephalogram epochs and outcome labels as inputs. Output of the network was the probability of good outcome. Data from two hospitals were used for training and internal validation (n = 661). Eighty percent of these data was used for training and cross-validation, the remaining 20% for independent internal validation. Data from the other three hospitals were used for external validation (n = 234). Prediction of poor outcome was most accurate at 12 hours, with a sensitivity in the external validation set of 58% (95% CI, 51-65%) at false positive rate of 0% (CI, 0-7%). Good outcome could be predicted at 12 hours with a sensitivity of 48% (CI, 45-51%) at a false positive rate of 5% (CI, 0-15%) in the external validation set. CONCLUSIONS: Deep learning of electroencephalogram signals outperforms any previously reported outcome predictor of coma after cardiac arrest, including visual electroencephalogram assessment by trained electroencephalogram experts. Our approach offers the potential for objective and real time, bedside insight in the neurologic prognosis of comatose patients after cardiac arrest.