Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1–3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.