The aim of this study was to examine the long-term effect of lung transplantation on Health Related Quality of Life by studying 28 patients who survived at least 55 months after lung transplantation. Measures included the Nottingham Health Profile, questions concerning lung-specific problems, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-Being, the Karnofsky performance index, and questions concerning activities of daily life. Furthermore, comorbid conditions were measured. Before transplantation patients reported restrictions on almost all quality of life measures. Until approximately 43 months after transplantation there were significant improvements on most dimensions of the Nottingham Health Profile and more patients could walk without dyspnea. Significant improvements occurred with regard to the levels of anxiety, depression, and well being, and the scores on the Karnofsky performance index improved. Activities of daily life could be performed without help by most patients. After approximately 43 months patients experienced more dyspnea, anxiety, depression, and a lower level of well being. The number of patients suffering from a decrease of kidney function, drug treated hyperlipidemia, insulin dependent diabetes mellitus and bronchiolitis obliterans syndrome increased. It may be concluded that patients experience a stable and better overall quality of life after transplantation. Long-term after lung transplantation patients experience a decline on several dimensions of quality of life, which may be explained by an increase of comorbid conditions and Bronchiolitis Obliterans Syndrome.