Aim: The optimal risk assessment model (RAM) to stratify the risk of venous thromboembolism (VTE) in medical inpatients is not known. We examined and compared how well the Padua Prediction Score (PPS) and the Caprini RAM stratify VTE risk in medical inpatients. Methods: We undertook a retrospective case-control study among medical inpatients admitted to a large general hospital in China during a 4-year period. In total, 902 cases were confirmed to have VTE during hospitalization and 902 controls were selected randomly to match cases by medical service. Results: The VTE risk increased significantly with an increase of the cumulative PPS or Caprini RAM score. A PPS and Caprini RAM high risk classification was, respectively, associated with a 5.01-fold and 4.10-fold increased VTE risk. However, the Caprini RAM could identify 84.3% of the VTE cases to receive prophylaxis according to American College of Chest Physicians guidelines, whereas the PPS could only identify 49.1% of the VTE cases. In the medical inpatients studied, five risk factors seen more frequently in VTE cases than in controls in the Caprini RAM were not included in the PPS. The Caprini RAM risk levels were linked almost perfectly to in-hospital and 6-month mortality. Conclusions: Both the PPS and Caprini RAM can be used to stratify the VTE risk in medical inpatients effectively, but the Caprini RAM may be considered as the first choice in a general hospital because of its incorporation of comprehensive risk factors, higher sensitivity to identify patients who may benefit from prophylaxis, and potential for prediction of mortality.