Continuous monitoring of high-risk patients and early prediction of severe outcomes is crucial to prevent avoidable deaths. Current clinical monitoring is primarily based on intermittent observation of vital signs and the early warning scores (EWS). The drawback is lack of time series dynamics and correlations among vital signs. This study presents an approach to real-time outcome prediction based on machine learning from continuous recording of vital signs. Systolic blood pressure, diastolic blood pressure, heart rate, pulse rate, respiration rate and peripheral blood oxygen saturation were continuously acquired by wearable devices from 292 post-operative high-risk patients. The outcomes from serious complications were evaluated based on review of patients’ medical record. The descriptive statistics of vital signs and patient demographic information were used as features. Four machine learning models K-Nearest-Neighbors (KNN), Decision Trees (DT), Random Forest (RF), and Boosted Ensemble (BE) were trained and tested. In static evaluation, all four models had comparable prediction performance to that of the state of the art. In dynamic evaluation, the models trained from the static evaluation were tested with continuous data. RF and BE obtained the lower false positive rate (FPR) of 0.073 and 0.055 on no-outcome patients respectively. The four models KNN, DT, RF and BE had area under receiver operating characteristic curve (AUROC) of 0.62, 0.64, 0.65 and 0.64 respectively on outcome patients. RF was found to be optimal model with lower FPR on no-outcome patients and a higher AUROC on outcome patients. These findings are encouraging and indicate that additional investigations must focus on validating performance in a clinical setting before deployment of the real-time outcome prediction.