Hospital readmission refers to the situation where a patient is re-hospitalized with the same primary diagnosis within a specific time interval after discharge. Hospital readmission causes $26 billion preventable expenses to the U.S. health systems annually and often indicates suboptimal patient care. To alleviate those severe financial and health consequences, it is crucial to proactively predict patients’ readmission risk. Such prediction is challenging because the evolution of patients’ medical history is dynamic and complex. The state-of-the-art studies apply statistical models which use static predictors in a period, failing to consider patients’ heterogeneous medical history. Our approach – Trajectory-BAsed DEep Learning (TADEL) – is motivated to tackle the deficiencies of the existing approaches by capturing dynamic medical history. We evaluate TADEL on a five-year national Medicare claims dataset reaching an F1 score of 87.3%. Our approach significantly outperforms all the state-of-the-art methods. Our findings suggest that health status factors and insurance coverage are important predictors for readmission. This study contributes to IS literature and analytical methodology by formulating the trajectory-based readmission prediction problem and developing a novel deep-learning-based readmission risk prediction framework. We also deliver implementable methods to assess patients’ readmission risk and take early interventions to avoid potential negative consequences.