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INTRODUCTION: ARDS contributes to high mortality and morbidity observed with coronavirus disease 2019 (COVID-19) Epoprostenol has antithrombotic, antiproliferative, and vasodilatory properties and improves respiratory parameters in ARDS The role of aerosolized epoprostenol (aEPO) in COVID-19 has not been evaluated We hypothesized that aEPO may improve oxygenation in intubated COVID-19 patients METHODS: We performed a single-center, retrospective, propensity-score matched cohort study A medical chart review was conducted for COVID-19 ARDS adult patients admitted between March 1, 2020 and May 1, 2020 Patients receiving aEPO (0 05 mcg/kg/minute) versus patients not receiving aEPO were matched for Rothman index and baseline PaO2:FiO2 (PF) ratios, and evaluated for effect of aEPO on PF ratio, gradient between arterial to end-tidal CO2, and dead space (primary endpoints) Secondary endpoints evaluated included in-hospital mortality, mechanical ventilation-free days, and ICU and hospital length of stay Safety endpoints evaluated included incidence of hypotension, significant bleeding, thrombocytopenia, and rebound hypoxemia RESULTS: Nineteen patients treated with aEPO were compared to 19 propensity-matched controls Baseline characteristics were well matched Management of ARDS was similar between groups The mean ± SD duration of aEPO treatment was 5 ± 2 8 days There were no significant differences in PF ratios between aEPO cohort and non-aEPO cohort at 3 hours (125 ± 56 vs 115 ± 40 mmHg), 6 hours (124 ± 41 vs 147 ± 73 mmHg), 12 hours (112 ± 39 vs 163 ± 62 mmHg), 24 hours (114 ± 33 vs 176 ± 64 mmHg), and 48 hours (150 ± 54 vs 212 ± 84 mmHg), although there was a trend toward higher PF ratios for the control group There were no significant differences in gradient between arterial to end-tidal CO2 and dead space between cohorts There were significantly more deaths in the control group compared to aEPO by day 10 (21% vs 0, p