Background: Cytoreductive nephrectomy (CN) for patients (pts) with metastatic renal cell carcinoma (mRCC) improved overall survival (OS) in the interferon (IFN) era, but the benefit of CN in the immune checkpoint inhibitor (ICI) era is unknown. Methods: We identified pts with mRCC receiving immunotherapy (IT) from 2004-2015 in the National Cancer Database (NCDB). Pts with partial nephrectomy or ablation were excluded. The ICI era was defined as 2013-2015 based on a high-profile publication in 2012 demonstrating efficacy of ICI in mRCC and the IFN era was defined as 2004-2005 due to FDA approval of sorafenib in 12/2005. Pts receiving CN with TKI were excluded, as prior NCDB study showed an OS benefit to CN in contrast to the results of the CARMENA trial. Univariable (UVA) and multivariable (MVA) associates with OS during each era were identified using Cox regression analysis including age, sex, race, income, insurance, treatment facility type, treatment location, clinical T stage (cT), clinical N stage (cN), histology, Fuhrman grade (FG), other metastectomy, and CN. Results: There was a 65% decline in mRCC pts receiving IT from 2005 to 2006 (end of the IFN era), which remained low (11% rise from 2006-2012) until a 93% rise from 2012 to 2013 (start of the ICI era). 128 of 422 (30.3%) pts in the IFN era received CN compared to 218 of 526 (41.4%) patients in the ICI era, p<0.001. Pts in each era were balanced with respect to median age, race, income, location, cT, and histology, but the ICI era had higher proportions of pts with private insurance, treatment at an academic center, N0 disease, FG 3-4, and other metastatectomy (p<0.05). Most pts with CN in the ICI era had IT after CN (89.9%); this was not coded in the IFN era. In the IFN era, CN compared to IT alone was associated with improved OS on UVA (HR 0.59, 95% CI 0.47-0.73, p<0.001) and MVA (HR 0.62, 95% CI 0.47-0.83, p=0.001). In the ICI era, CN compared to IT alone was associated with improved OS on UVA (HR 0.63, 95% CI 0.49-0.81, p<0.001) but not on MVA (0.82, 95% CI 0.58-1.14, p=0.234). Conclusions: Despite increased utilization of CN for US pts with mRCC treated with IT during the ICI era, the lack of OS benefit in recent years suggests a need for prospective reevaluation of the value CN and its timing with ICI.