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Chronic lung allograft dysfunction (CLAD) is the primary cause of late graft loss after lung transplantation, affecting up to half of lung transplant recipients within 5 years and presenting with heterogeneous phenotypes, most commonly bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome. Prevention and treatment of CLAD are challenging. This European Society for Organ Transplantation (ESOT) clinical practice guideline was developed by a multidisciplinary Task Force, including patient and allied healthcare representation, using systematic reviews and GRADE methodology. Eight key PICO questions addressing prevention and treatment of CLAD were evaluated. In terms of prevention, recommendations are in favor of using tacrolimus over cyclosporine, either mycophenolate or azathioprine, and azithromycin to reduce the risk of CLAD. Regarding treatment, montelukast could be considered in early-stage BOS. Current data are inconclusive in demonstrating benefits of anti-thymocyte globulin, alemtuzumab or extracorporeal photopheresis compared with standard of care, and do not support the use of antifibrotics in BOS. The Task Force emphasizes the urgent need for high-quality clinical trials and standardized care pathways in CLAD management.