COVID-19 has resulted in inpatient hospitalizations and death. Anti-spike monoclonal antibodies, including bamlanivimab, have resulted in a reduction in hospitalization rates in clinical trials. A study was conducted across a single healthcare system of non hospitalized patients aged 18 years or older with positive severe acute respiratory syndrome coronavirus 2 testing or suffering from risk factors for severe COVID-19. Patients who received bamlanivimab order filled an order placed but did not receive it; firstly, it came out to be a 30-day hospitalization rate from initial positive coronavirus 2 polymerase chain reaction. Multivariable logistic regression was used for examination to calculate independent associations with 30-day hospitalization. Between 30th November 2020 and 19th January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive the drug (controls). The thirty-day hospitalization rate was lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21–.64, P<.001), and the number needed to treat was 8. Odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19, 95% CI: 1.31–2.16, P<.001; OR 1.68, 95% CI: 2.12–8.30, P<.001, respectively). Therefore, to prevent hospitalization associated with coronavirus disease using bamlanivimab remains unclear.