BACKGROUND: We aimed to build a model using machine learning for the prediction of survival in trauma patients and compared these model predictions to those predicted by the most commonly used algorithm, the Trauma and Injury Severity Score (TRISS). METHODS: Enrolled hospitalized trauma patients from 2009 to 2016 were divided into a training dataset (70% of the original data set) for generation of a plausible model under supervised classification, and a test dataset (30% of the original data set) to test the performance of the model. The training and test datasets comprised 13,208 (12,871 survival and 337 mortality) and 5603 (5473 survival and 130 mortality) patients, respectively. With the provision of additional information such as pre-existing comorbidity status or laboratory data, logistic regression (LR), support vector machine (SVM), and neural network (NN) (with the Stuttgart Neural Network Simulator (RSNNS)) were used to build models of survival prediction and compared to the predictive performance of TRISS. Predictive performance was evaluated by accuracy, sensitivity, and specificity, as well as by area under the curve (AUC) measures of receiver operating characteristic curves. RESULTS: In the validation dataset, NN and the TRISS presented the highest score (82.0%) for balanced accuracy, followed by SVM (75.2%) and LR (71.8%) models. In the test dataset, NN had the highest balanced accuracy (75.1%), followed by the TRISS (70.2%), SVM (70.6%), and LR (68.9%) models. All four models (LR, SVM, NN, and TRISS) exhibited a high accuracy of more than 97.5% and a sensitivity of more than 98.6%. However, NN exhibited the highest specificity (51.5%), followed by the TRISS (41.5%), SVM (40.8%), and LR (38.5%) models. CONCLUSIONS: These four models (LR, SVM, NN, and TRISS) exhibited a similar high accuracy and sensitivity in predicting the survival of the trauma patients. In the test dataset, the NN model had the highest balanced accuracy and predictive specificity.