Background: Evidence remains inconclusive on any significant benefits of remdesivir in patients with mild-to-moderate COVID-19. This study explored the disease progression, various clinical outcomes, changes in viral load, and costs associated with early remdesivir treatment among COVID-19 patients. Methods: A territory-wide retrospective cohort of 10 419 patients with COVID-19 hospitalized from 21 January 2020 to 31 January 2021 in Hong Kong was identified. Early remdesivir users were matched with controls using propensity-score matching in a ratio ≤1:4. Study outcomes were time to clinical improvement of at least 1 point on WHO clinical progression scale, hospital discharge, recovery, viral clearance, low viral load, positive IgG antibody, in-hospital death, and composite outcomes of in-hospital death requiring invasive ventilation or intensive care. Results: After multiple imputation and propensity-score matching, median follow-up was 14 days for both remdesivir (n = 352) and control (n = 1347) groups. Time to clinical improvement was significantly shorter in the remdesivir group than that of control (HR: 1.14; 95% CI: 1.01–1.29; P = .038), as well as for achieving low viral load (1.51; 1.24–1.83; P < .001) and positive IgG antibody (1.50; 1.31–1.70; P < .001). Early remdesivir treatment was associated with lower risk of in-hospital death (HR: .58; 95% CI: .34–.99; P = .045), in addition to a significantly shorter length of hospital stay (difference: −2.56 days; 95% CI: −4.86 to −.26; P = .029), without increasing risks of composite outcomes for clinical deterioration. Conclusions: Early remdesivir treatment could be extended to hospitalized patients with moderate COVID-19 not requiring oxygen therapy on admission.