Background: SARS-CoV-2 was declared a global pandemic and public health emergency by the WHO in January 2020. Infected cancer patients have more than a 3-fold risk of adverse events including pneumonitis, ARDS, and mortality. The FDA approved two monoclonal antibodies (MAbs), casirivimab/imdevimab and bamlanivimab, for treating mild/moderate COVID-19. In this real-world retrospective study, we aim to evaluate the efficacy of monoclonal antibody therapy in patients with and without a history of malignancy. Methods: Through retrospective review, we identified patients who received MAbs for COVID-19 at UT Southwestern Medical Center from December 2020 to July 2021. We collected data on patient demographics, oncology history, COVID-19 infection history, vaccination status, type of MAb infused, post-infusion adverse events and hospitalization. We performed univariate analysis with Fishers exact test and multivariate logistic regression analysis of unvaccinated patients to assess the impact of malignancy history along with other factors on hospitalization rates. Results: A total of 395 patients received MAbs, of which 275 (70%) were white, 42 (11%) were vaccinated with the first dose, and 6 (1%) with the second dose against COVID-19. 128 (33%) patients had a history of malignancy, and 68 (53%) were diagnosed with solid tumors. Of the cancer patients, 112 (87%) were on or had therapy (chemotherapy, immunotherapy, and/or radiation). Table 1 describes the risk of all cause hospitalization within one month of MAbs. Patients who received casirivimab/imdevimab had reduced hospitalization at one-month post-infusion (OR 0.18; p: <0.01; CI: 0.05-0.5) while patients receiving bamlanivimab had an OR of 0.49 (p=0.06, CI: 0.23-1.04). History of malignancy (p=0.67; CI 0.55-2.42), exposure to chemotherapy (p=0.06), and immunotherapy administration (p=1) did not impact the risk of hospitalization post-infusion. Conclusions: MAbs proved critical in the management of COVID-19 patients, limiting disease intensity and progression. In our real-world data (RWD) of 395 patients receiving MAbs, we found significant benefit of reduced hospitalization up to one month post-infusion, irrespective of patients' history of malignancy or treatments. With current data showing hampered antibody response of some immunocompromised patients with malignancy, our RWD provides key information on application of MAbs in reducing hospitalization for those at-risk populations.