BACKGROUND: RADAR compared REG1 (25%, 50%, 75%, 100% reversal) with unfractionated heparin (UFH) in 640 acute coronary syndrome (ACS) patients (479 REG1 patients, 161 UFH patients) undergoing an invasive management strategy. We sought to determine whether the REG1 anticoagulation system allows for safer early arterial sheath removal following cardiac catheterization. METHODS: REG1 patients had arterial sheath removal immediately post catheterization. We measured arterial sheath management outcomes and vascular access complications in patients who had sheath removal without vascular closure device implantation; 461 patients were included (349 REG1 patients, 112 UFH patients). RESULTS: The median (25th, 75th) time from end of catheterization to arterial sheath removal was shorter in REG1 arms regardless of reversal strategy (26 minutes [18, 46]) compared with UFH (210 minutes [102, 342]). There was no increase in median time from sheath removal to hemostasis (10 minutes [10, 20] and 10 minutes [10, 20]; P=.60); vascular access-site bleeding complications were numerically fewer with REG1 than UFH (6% vs 11%; odds ratio [OR], 0.57; 95% CI, 0.27-1.18; P=.14). There were no differences in time to ambulation or hospital length of stay between the groups. CONCLUSIONS: REG1 allows for very early arterial sheath removal following cardiac catheterization without increasing the time to hemostasis or vascular access-site bleeding complications. Further studies are needed to determine whether anticoagulation with REG1 will translate into shorter hospital lengths of stay and reduced costs in ACS patients.