Background: There is a scarcity of data on outcomes and predictors of therapeutic failure of mAbs in frail COVID-19 patients. Methods: Prospective study including consecutive COVID-19 outpatients referred by primary care physicians for mAbs treatment. Outcomes evaluated were 60-day mortality, time to SARS-CoV-2 clearance, need for hospitalization, and O2-therapy. Results: Among 1026 COVID-19 patients enrolled, 60.2% received casirivamab/imdevimab and 39.8% sotrivimab. Median age was 63 years, 52.4% were males and median time from positive nasopharyngeal swab to mAbs administration was 3 days [IQR, 2-5]. 78.1% were vaccinated. Overall, 60-day mortality was 2.14%. No differences in outcomes were observed between the two mAbs used. No difference was observed in mortality between vaccinated and unvaccinated patients (p=0.925), although lower rate of hospitalization (p