Persistent alveolar air leak (PAAL) after major lung resection remains a common complication in thoracic surgery. The aim of this study was to identify a subset of patients with high risk of developing PAAL after pulmonary lobectomy. Another objective was to evaluate the influence of PAAL on postoperative complications and length of hospital stay. A retrospective analysis on 895 patients undergoing pulmonary lobectomy from January 2014 to December 2019 was performed. PAAL was defined as air leak lasting more than 5 days after lung surgery. Univariate analyses and logistic regressions were performed to identify the predictors of PAAL. A backward selection algorithm was used to identify the optimal set of predictors. The incidence of PAAL was 8.2% (74/895). Male gender (p=0.017), BMI (p<0.001), transient ischemic attack (p=0.031), FEV1 (p=0.018), lobectomy combined with adjacent subsegmentectomy (p=0.018), partial and extended pleural adhesions (p=0.033 and p=0.038, respectively) were identified as independent risk factors for PAAL through logistic regression. A weak positive correlation was found between video-assisted thoracic surgery (VATS) and PAAL following pulmonary lobectomy (p=0.100). PAAL was found to be associated with higher risk of postoperative morbidity (p=0.002) and with longer hospital stay (p<0.001). Both preoperative and intraoperative risk factors may be responsible for PAAL after pulmonary lobectomy. VATS does not appear to prevent this postoperative complication. An alveolar air leak lasting beyond 5 days after pulmonary lobectomy is associated with worse postoperative outcomes.