Background <p>Control of pleural cavity pressure after pneumonectomy is essential to prevent early hemodynamic and respiratory complications related to mediastinal shift. This study aimed to assess early postoperative adverse events according to the residual pleural cavity management strategy used.</p> Methods <p>We performed a retrospective multicenter study including patients who underwent pneumonectomies for malignant disease via thoracotomy between 2004 and 2024 in three centers. Each center historically used a single pleural cavity management strategy: no drainage (NO DRAIN group), clamped pleural drainage (CLAMPED group), or drainage connected to a pressure-balancing system (BALANCED group).</p> Results <p>Overall, 304 patients were included: 106 in the NO DRAIN group, 106 in the CLAMPED group, and 92 in the BALANCED group. Four cases (1.3%) of hemodynamic or respiratory failure related to mediastinal shift occured: in the NO DRAIN group, one cardiopulmonary arrest immediately after air aspiration from the residual pleural cavity on postoperative day-one; in the CLAMPED group, two tamponades on postoperative day-2; in the BALANCED group, one acute respiratory distress with extensive subcutaneous emphysema on postoperative day-two. None of these events were fatal. Rates of atrial fibrillation (27% vs. 14% and 11%, p&lt;0.01) and reoperation (20% vs 7% and 13%, p=0.017), as well as length of hospital stay (11.3 days vs 9.8 and 8.4, p&lt;0.001), were higher in the CLAMPED group. One-month survival did not differ significantly between groups (94%, 95%, and 99%, p = 0.19).</p> Conclusion <p>Early mediastinal shift- related complications after pneumonectomy are uncommon and may occur regardless of pleural cavity management strategy. The clamped-drain strategy may be associated with increased postoperative arrhythmia.</p>