Background and aims Thoracic air leak syndrome (TALS) is a complication related to chronic pulmonary graft-versus-host disease (pGvHD) that affects approximately 0.83% to 3.08% patients after allogenic hematopoietic stem cell transplant. Such complication is defined as the occurrence of any form of air leak in the thorax, including spontaneous pneumomediastinum or pneumopericardium, subcutaneous emphysema, interstitial emphysema and pneumothorax and has a negative impact on post-transplant survival. The aim of the present study is to describe a single-center experience in the surgical management of recurrent TALS in adolescents and young adults and its outcome. Methods We retrospectively reviewed the clinical notes of patients with previous allogenic hematopoietic stem cell transplant who underwent surgical procedures for recurrent TALS from January 2016 until March 2021. As well we analyzed clinical data, number of episodes of thoracic air leak, surgical procedures and relative outcome. Results In the examined period, four patients, aged 16 to 25 years, underwent surgical procedures for TALS, including thoracostomy tube placement, thoracoscopic pleurodesis and thoracotomy. All the patients had been diagnosed with pGvHD before the onset of TALS, with a mean time lapse of 276 days (range 42 – 513). These patients experienced on average 4.5 air leak episodes (range 3 – 6). All the patients experienced at least two episodes before surgery. One patient underwent emergency tube thoracostomy only, three patients underwent thoracoscopic pleurodesis and two patients underwent thoracotomy. After surgery, patients were free from air leak symptoms for a mean time of 176 days (range 25 – 477). Pulmonary function progressively deteriorated, and all the patients eventually died because of respiratory failure after a mean time of 483 days (range 127 – 1045) after the first episode of air leak. Conclusions Surgery provides temporary relief to symptoms related to TALS. When TALS develops, pulmonary function progressively worsens toward respiratory failure and death.