e16520 Background: Adrenergic receptors (ADR) have a well-established role in kidney physiology, suggesting a possible role of ADR signaling in renal cell carcinoma (RCC). Preclinical studies have shown a possible anti-tumor effect of both alpha-adrenergic blockers (AB) and beta-adrenergic blockers (BB) on renal cancer cells. However, the literature is conflicting regarding the effect on clinical outcomes. In addition, there is no comprehensive analysis of what role these medications have specifically in RCC patients with metastatic disease. In this single health system retrospective study, we evaluate the effect of AB or BB prescription on cancer-specific outcomes in patients with metastatic RCC. Methods: Clinical data was abstracted from the electronic health record and the institutional cancer registry at The Mount Sinai Health System to include patients with RCC diagnosed with metastatic disease ( de novo or relapsed) between 2016-2020. Follow up data was recorded until a data lock of 4/1/2021. Multivariate Cox regression was used to evaluate the association of AB and BB prescription on overall survival (OS) for the entire cohort and progression free survival (PFS) for patients who received any first line therapy. Multivariate logistic regression was used to evaluate association of these medications with overall response rate (ORR) of first line therapies with available data on initial response. Analyses were controlled for clinical risk factors including age at diagnosis, sex, race, treatment plan including immunotherapy, and medical history of benign prostatic hyperplasia, hypertension, or heart failure. Data was analyzed using R version 4.1.0. Results: 133 patients were identified for inclusion in the study. 61% of cases are de novo metastatic and 39% are relapsed from previously resected disease. 71% are clear cell histology, 3.8 % are papillary, and the rest are unspecified/other. 84 patients (63%) received at least a 1 st line systemic therapy. AB or BB prescription alone is not associated with OS, PFS, or ORR. However, prescription of both AB and BB is associated with worse OS (HR 2.94 95% CI 1.13-7.68), worse PFS (HR 7.70 95% CI 1.80-33.0), and decreased odds of responding to 1 st line therapy (OR 0.06 95% CI 0.00-0.55) on multivariate analysis. Conclusions: The data suggests that the concurrent use of both an AB and BB in patients with metastatic RCC leads to worse clinical outcomes. What remains unclear is if there is a negative synergistic effect of these medications on RCC pathophysiology or if the prescription of these medications is associated with another negative confounding clinical factor. Since these medications are commonly utilized for cardiovascular disease, multivariate analyses attempted to control for these comorbidities. Future studies may add to this data by cataloging the severity of heart failure and doses of AB and BB medications used in a RCC cohort.