To investigate the causes and prevention measures of severe bleeding complicating minimally invasive percutaneous nephrolithotomy. METHODS: Retrospective analysis of clinical data of 53 cases admitted from January 2005 to January 2010 with severe bleeding from minimally invasive percutaneous nephrolithotomy. Results: The causes of bleeding were: 6 cases of improper puncture bleeding, 15 cases of channel dilatation bleeding, 11 cases of too deep puncture, 15 cases of collection system laceration bleeding during lithotripsy, 3 cases of infection or sepsis, 1 case of intercostal vessel injury, and 2 cases of nephrostomy tube prolapse. 51 cases were cured by conservative treatment, and 2 cases were treated by superselective renal artery intervention embolization. There was no recurrent bleeding and no death or nephrectomy. Conclusion: Recognizing the various causes of bleeding in minimally invasive percutaneous nephrolithotomy, standardizing intraoperative operation, careful postoperative observation, accurate determination of the cause of bleeding and active treatment are important for the prevention and treatment of severe bleeding in minimally invasive percutaneous nephrolithotomy.