Purpose Two randomized trials published in 2001 provided level 1 evidence for the use of cytoreductive nephrectomy (CyNx) for the treatment of metastatic renal cell carcinoma (mRCC). However, the regulatory approval of vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) in 2005 has left an “evidence void” regarding the use of CyNx. We evaluated the patterns in the use of CyNx in the cytokine and VEGFR-TKI eras, and the patient characteristics associated with the use of CyNx. Methods The Surveillance, Epidemiology, and End Results registry was used to identify patients with histologically or cytologically confirmed stage IV RCC between 2001 and 2008. Patients were classified as treated during the cytokine (2001–2005) or VEGFR-TKI (2006–2008) eras. A multivariate logistic regression analysis was performed to calculate the odds of undergoing CyNx according to treatment era and socioeconomic characteristics. Results Overall, 1,112 of 2,448 patients (45 %) underwent CyNx. CyNx use remained stable between 2001 and 2005 (50 %), but decreased to 38 % in 2008. Logistic regression analysis revealed that older age (OR 0.82, 95 % CI: 0.68, 0.99), black race (OR 0.64, 95 % CI: 0.46, 0.91), Hispanic ethnicity (OR 0.71, 95 % CI: 0.54, 0.93), and treatment in the VEGFR-TKI era (OR 0.82, 95 % CI: 0.68, 0.99) were independently associated with decreased use of CyNx. Conclusions Use of CyNx in the United States has declined in the VEGFR-TKI era. Older patients and minorities are less likely to receive CyNx. Results of ongoing phase III trials are needed to refine the role of this treatment modality.