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Remdesivir is the only antiviral approved for lower respiratory tract infection produced by SARS-CoV-2. The main objective of this study was to determine the mortality rate, readmissions, mean hospital stay, need for higher levels of oxygen support, and adverse effect-induced abandonment rate in hospitalized patients diagnosed with COVID-19 and treated with remdesivir (RDSV). The secondary objective was to determine mortality-related risk factors in these patients. The study included a prospective cohort of patients admitted to a third level Spanish hospital between July 5, 2020 and February 3, 2021 for COVID-19 diagnosed by SARS-CoV-2 polymerase chain reaction and/or antigen test and treated with RDSV. Remdesivir was received by 185 patients (69.7% males) with a mean age of 62.5 years, median Charlson index of 3 (interquartile range [IQR]: 1–4), and median ambient air oxygen saturation of 91% (IQR: 90–93); 61.6% of patients had hyper-inflammatory syndrome at admission. Median time with symptoms before RDSV treatment was 5 days (IQR: 3–6) and the median hospital stay was 10 days (IQR: 7–15); 19 patients (10.3%) died after a median stay of 13.5 days (IQR: 9.7–24 days), 58 patients (12.9%) were admitted to ICU, 58 (31.4%) needed higher levels of oxygen support, 0.5% abandoned the treatment due to adverse effects, and there were no readmissions. The only mortality-related factor was the need for higher levels of oxygen support (odds ratio 12.02; 95% confidence interval 2.25–64.2). All studied patients were admitted to hospital with a diagnosis of COVID-19 and in respiratory failure, needing initial low-flow oxygen support, and all received RDSV within 1 week of symptom onset. The percent mortality was lower in these patients than was observed in all patients with severe COVID-19 admitted to our center (10.3% vs 20.3%, respectively). Despite receiving RDSV, 1 in 3 patients needed higher levels of oxygen support, the sole mortality-related factor.