BACKGROUND: It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. METHODS: We used data from TriNetX, a global federated health research network. Patients aged >/=18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). RESULTS: 738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 +/- 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12-1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64-1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91-5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54-1.51; Log-Rank test p = 0.513). CONCLUSION: In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.