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ABSTRACTBackground There were increased claims of thrombotic events in ICU-bound patients with COVID-19. We designed this observational study to examine implementation of systemic anti-coagulation on arterial catheter failure (ACF) and to identify contributing risk factors.Methods A total of 245 COVID-19 subjects were included in this observational study, 48 patients in the non-systemic, (Non-SA), anticoagulation cohort, and 197 patients in the systemic (SA), anticoagulation group. The first arterial line inserted on ICU admission for every patient was monitored regarding its duration of patency, number and location of consecutive arterial lines inserted during stay in ICU. Demographics of patients, ICU parameters and risk factors for ACF were analyzed.Results The percentage of ACF was significantly higher in Non-SA group, 45.8 % when compared to SA group, 25.9%, P = 0.007. The patients with ACF exhibited higher D-dimer, co-morbidities, diabetic patients, received aspirin and mortality than the patent group, respectively, p = 0.002, p = 0.002, p < 0.0001, p < 0.0001, and p < 0.0001. This group also received higher sedation and vasopressors consumption and more prone position on mechanical ventilation, respectively, p < 0.0001, p < 0.0001, and p < 0.0001 when compared to patent group. They had prolonged length of stay in ICU and hospital, respectively, p = 0.001 and p = 0.042. The cumulative incidence of index ACF was (Log-rank test 6.95, P = 0.008) when comparing SA group versus non-SA group, respectively, P = 0.007. On Cox-proportional hazard multivariate regression analysis, independent predictors of ACF were: platelets level (per 100.000 increase), (HR 1.40; 95% CI 1.12–1.74; p = 0.003), blind technique versus ultrasound in arterial line insertion (HR 4.12; 95% CI 1.60–10.67; p = 0.003), and prone position in ICU (HR 2.07; 95% CI 1.180–3.63; p = 0.011).Conclusion We observed three independent predictors of arterial line failure including platelets level and ultrasound use during arterial catheter insertion and prone position in ICU. Systemic anticoagulation was associated with more patency of arterial catheter than prophylactic therapy group.