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Health-related quality of life (HRQoL) represents an important outcome measure to assess the success of transplantation in the long term. This study evaluated HRQoL in heart (HTx) and lung (LTx) transplant survivors, and assessed potential outcome-related predictors from before to 5 years after transplantation.Study participants (n=170) were prospectively followed up from before to 5 years after HTx (n=82) or LTx (n=88), including HRQoL assessments (pretransplantation, 6, 12, and yearly between 24 and 60 months) using the Short Form-36, employment status index, and monitoring of adverse events.Patient groups (HTx vs. LTx) differed with respect to gender (men 74% vs. 48%; P<0.03) and high-urgency waiting status (72% vs. 45%; P<0.0001). Both cohorts showed the most significant HRQoL improvements within the first year posttransplant (P<0.0001), and relatively stable conditions afterward. Marital (P<0.01) and employment status (P<0.01) impacted HRQoL in both groups. The incidence of bronchiolitis obliterans showed significantly lower HRQoL in LTx patients (29.3%; P<0.005).HTx and LTx patients benefit from the transplant procedure with respect to HRQoL improvements for at least 5 years posttransplant; however, their trajectories during this time interval differ. Further research on organ-type–related predictors of HRQoL is necessary for the development of tailored psychosocial interventions.