Postoperative pulmonary complications have a deleterious impact in regards to thoracic surgery. Pneumonectomy is associated with the highest perioperative risk in elective thoracic surgery. The data from 152 patients undergoing pneumonectomy in this multicenter retrospective study were extracted from the German Thorax Registry database and presented after univariate and multivariate statistical processing. This retrospective study investigated the incidence of postoperative pulmonary complications (PPCs) and their impact on perioperative morbidity and mortality. Patient-specific, preoperative, procedural, and postoperative risk factors for PPCs and in-hospital mortality were analyzed. A total of 32 (21%) patients exhibited one or more PPCs, and 11 (7%) died during the hospital stay. Multivariate stepwise logistic regression identified a preoperative FEV1 < 50% (OR 9.1, 95% CI 1.9–67), the presence of medical complications (OR 7.4, 95% CI 2.7–16.2), and an ICU stay of more than 2 days (OR 14, 95% CI 3.9–59) as independent factors associated with PPCs. PPCs (OR 13, 95% CI 3.2–52), a preoperative FEV1 < 60% in patients with previous pulmonary infection (OR 21, 95% CI 3.2–52), and continued postoperative mechanical ventilation (OR 8.4, 95% CI 2–34) were independent factors for in-hospital mortality. Our data emphasizes that PPCs are a significant risk factor for morbidity and mortality after pneumonectomy. Intensified perioperative care targeting the underlying risk factors and effects of PPCs, postoperative ventilation, and preoperative respiratory infections, especially in patients with reduced pulmonary reserve, could improve patient outcomes.