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BACKGROUND: Postsurgical pleural infection is a life-threatening complication after implantation of artificial devices such as ventricular assist devices (VADs). The treatment can be challenging and the evidence in the literature is very limited. Here we report our multidisciplinary approach of the management of pleural infection after VAD implantation. METHODS: Between March 2014 and December 2019, 33 patients developed postoperative pleural infection after VAD implantation and underwent thoracic surgical intervention at our institution. All patients were prospectively enrolled in this analysis. Data were retrospectively analyzed. Primary outcome was the 90-day mortality rate. Length of ICU stay related to pleural infection, chest tube duration, re-thoracotomy rate and length of ventilatory support represented secondary outcomes. RESULTS: The 90-day mortality rate was 6% (2 patients). The mean ICU stay related to the pleural infection was 6 days (2–24 days). Video-assisted thoracoscopic surgery (VATS) was performed in all patients. Conversion to thoracotomy was necessary in 12 cases. Decortication and parietal pleurectomy in addition to hematoma and empyema removal was performed in all patients. Due to diffuse bleeding, packing of the thoracic cavity with temporary thoracic closure was necessary in 10 patients. Depacking was performed after a mean of 3 days (3–7 days). Recurrent empyema or bleeding after definitive chest closure was not observed. Lung resection was performed in 3 patients. CONCLUSIONS: Thoracic surgical management of pleural infection in patients after VAD implantation is challenging and complicated due to the inevitable anticoagulative therapy. A perioperative multidisciplinary management which includes the early involvement of thoracic surgical expertise helps to improve survival in this very complex patient cohort.