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Lung transplantation (LT) increases the life expectancy of patients affected by end stage pulmonary disease; specifically, its ultimate aims are to improve survival and health related quality of life (HRQoL). The aim of the present longitudinal study was to determine the HRQoL trajectory and changes in functional capacity from time of entry in the waiting list for LT to 2 year after LT. The study included sixty-nine outpatients enrolled in a single medical center when they entered the waiting list for LT and who subsequently received it. They were then followed up over 2 years after LT. HRQoL was assessed by the physical and mental component summary (PCS and MCS) scores of the 36-item Short Form Health Survey (SF-36) and Saint George’s Respiratory Questionnaire (SGRQ). Psychological distress was evaluated with the General Health Questionnaire (GHQ), and functional capacity was investigated using the six-minute walk test (6MWT) and forced expiratory volume (FEV1). Patients showed low SF-36 PCS (30.5±7.8) and SGRQ total (61.8±17.5) scores at entry in the waiting list, but exhibited significant changes over time after LT (p<0.001). Furthermore, patients who showed an increase of at least 50% in SF36 PCS and SGRQ scores at 6 months survived longer. Both FEV1 and 6MWT distance as well as GHQ scores significantly changed over time, with improvements occurring in the first 6 months after LT but no major changes thereafter. Out of the 69 patients enrolled, 32 died over a median follow-up of 51 months. Although mortality tended to be slightly higher for patients with lower HRQoL at the baseline assessment, this difference was not statistically significant. HRQoL evaluations appear critical in the follow-up of LT candidates, in particularly SGRQ, because of its specificity in targeting respiratory symptoms and functional wellbeing.