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INTRODUCTION: In cases of empyema, some form of intervention, either chest tube drainage, thoracoscopy, video-assisted thoracic surgery (VATS), or thoracotomy, with or without pleural fibrinolysis, is required. What the best approach is and when and how to intervene is a matter of debate. STUDY OBJECTIVE: To analyze the safety and outcome of medical thoracoscopy in the treatment of multiloculated empyema. METHODS: We report a retrospective series of 127 patients with thoracic empyema treated with medical thoracoscopy from 1989 to 2003 in three hospitals in Switzerland and Italy. All patients had multiloculated empyema as identified by chest ultrasonography. In the absence of multiloculation, or in case of fibrothorax, simple chest tube drainage or surgical VATS/thoracotomy were performed, respectively. RESULTS: Mean age +/- SD was 58 +/- 18 years (range, 9 to 93 years). In 47%, a microbiological diagnosis was made. Complications occurred in 9% of patients (subcutaneous emphysema, n = 3; air leak of 3 to 7 days, n = 9). No mortality was observed. Forty-nine percent of patients received postinterventional intrapleural fibrinolysis. Medical thoracoscopy was primarily successful in 91% of cases. In four patients, the insertion of an additional chest tube or a second medical thoracoscopy was required. Finally, 94% of patients were cured by nonsurgical means. Six percent of patients required surgical pleurectomy, mostly through thoracotomy. CONCLUSION: Multiloculated empyema as stratified by ultrasonography can safely and successfully be treated by medical thoracoscopy.