Background Predictive machine learning models have made use of a variety of scoring systems to identify clinical deterioration in ICU patients. However, most of these scores include variables that are dependent on medical staff examining the patient. We present the development of a real-time prediction model using clinical variables that are digital and automatically generated for the early detection of patients at risk of deterioration. Methods Routine monitoring data were used in this analysis. ICU patients with at least 24 h of vital sign recordings were included. Deterioration was defined as qSOFA ≥ 2. Model development and validation were performed internally by splitting the cohort into training and test datasets and validating the results on the test dataset. Five different models were trained, tested, and compared against each other. The models were an artificial neural network (ANN), a random forest (RF), a support vector machine (SVM), a linear discriminant analysis (LDA), and a logistic regression (LR). Results In total, 7156 ICU patients were screened for inclusion in the study, which resulted in models trained from a total of 28,348 longitudinal measurements. The artificial neural network showed a superior predictive performance for deterioration, with an area under the curve of 0.81 over 0.78 (RF), 0.78 (SVM), 0.77 (LDA), and 0.76 (LR), by using only four vital parameters. The sensitivity was higher than the specificity for the artificial neural network. Conclusions The artificial neural network, only using four automatically recorded vital signs, was best able to predict deterioration, 10 h before documentation in clinical records. This real-time prediction model has the potential to flag at-risk patients to the healthcare providers treating them, for closer monitoring and further investigation.