OBJECTIVES: Limited data are available on the health-related quality of life (HRQOL) of patients with metastatic renal cell carcinoma (mRCC) in daily practice. The aim of this study was to estimate HRQOL of patients with mRCC in daily practice, and to assess the influence of patient- and disease characteristics, such as comorbidities and adverse events on HRQOL. METHODS: Patients with mRCC were selected from a Dutch population-based registry (PERCEPTION). In this RCC registry, data were collected on patient- and disease characteristics, treatments and adverse events. To measure HRQOL, a generic questionnaire (EQ-5D) was used. Multiple linear regression was used to determine which patient- and disease characteristics were associated with HRQOL.  RESULTS: In this study, 100/465 (21.5%) patients presented with or progressed to mRCC. Average age at diagnosis was 62.9 years (range: 40-82) and 77% was male. Patients with mRCC reported an average EQ-5D utility score of 0.73 (95%CI: 0.64-0.82) at diagnosis. Two to six months after diagnosis, the average EQ-5D utility score was 0.75 (95%CI: 0.66-0.84) (P=0.319). Multiple linear regression showed that presence of comorbidities (>1), number of metastatic sites (>1), radiotherapy and presence of grade 3 or grade 4 toxicity were significantly associated with a lower EQ-5D utility score. Although presence of bone metastases significantly lowered the EQ-5D utility score, this factor was not significant after adjustment for other factors.  CONCLUSIONS: This is one of the first studies that provides insights into the HRQOL of patients with mRCC in daily practice. In contrast to previous studies, this study also identified patient- and disease characteristics that influence HRQOL. Presence of comorbidities, number of metastatic sites, radiotherapy and presence of severe toxicity related to targeted therapies were significantly associated with HRQOL. This information is helpful in correcting EQ-5D utility scores for these characteristics, and will be useful in future cost-effectiveness analyses.