Risk prediction tools are increasingly popular aids in clinical decision-making. However, the underlying models are often trained on data from general patient cohorts and may not be representative of and suitable for use with targeted patient groups in actual clinical practice, such as in the case of osteoporosis patients who may be at elevated risk of mortality. We developed and internally validated a cardiovascular mortality risk prediction model tailored to individuals with osteoporosis using a range of machine learning models. We compared the performance of machine learning models with existing expert-based models with respect to data-driven risk factor identification, discrimination, and calibration. The proposed models were found to outperform existing cardiovascular mortality risk prediction tools for the osteoporosis population. External validation of the model is recommended.Clinical Relevance- This study presents the performance of machine learning models for cardiovascular death prediction among osteoporotic patients as well as the risk factors identified by the models to be important predictors.