Accumulating studies appear to suggest that the risk factors for venous thromboembolism (VTE) among young-middle-aged inpatients are different from those among elderly people. Therefore, the current prediction models for VTE are not applicable to young-middle-aged inpatients. The aim of this study was to develop and externally validate a new prediction model for young-middle-aged people using machine learning methods. The clinical data sets linked with 167 inpatients with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 406 patients without DVT or PE were compared and analysed with machine learning techniques. Five algorithms, including logistic regression, decision tree, feed-forward neural network, support vector machine, and random forest, were used for training and preparing the models. The support vector machine model had the best performance, with AUC values of 0.806–0.944 for 95% CI, 59% sensitivity and 99% specificity, and an accuracy of 87%. Although different top predictors of adverse outcomes appeared in the different models, life-threatening illness, fibrinogen, RBCs, and PT appeared to be more consistently featured by the different models as top predictors of adverse outcomes. Clinical data sets of young and middle-aged inpatients can be used to accurately predict the risk of VTE with a support vector machine model.