Patients with mechanical heart valves are still not eligible for treatment with direct oral anticoagulants (DOAC). We aimed to conduct a proof-of-principle study investigating the anti-Xa inhibitor rivaroxaban as antithrombotic treatment in patients with recent mechanical aortic valve replacement. Low-risk patients scheduled for elective mechanical aortic valve replacement were treated with rivaroxaban 20 mg once daily (OD) in a prospective cohort study, started on day 3 postoperatively and given for 6 months. The study was registered at ClinicalTrials.gov (#NCT02128841). Ten patients were included (median age, 48; range 39 to 60). Indication was aortic valve stenosis in 6 patients, aortic root aneurysm with severe aortic valve regurgitation in 3 patients, and mixed stenosis/regurgitation in 1 patient. Neither thromboembolic nor bleeding events were observed, and no patient died. Absence of valve thrombosis was demonstrated in all patients. On day 7, median D-dimers were 2723 μg/L (inter-quartile range [IQR] 1672, 5695 μg/L), median TAT levels were 4.5 μg/L (IQR 4.1, 5.6 μg/L); and median peak thrombin generation was 150 nM (IQR 91, 183). On day 90, median D-dimers were 426 μg/L (IQR 278, 569), median TAT levels were 2.7 μg/L (IQR 2.2, 3.1), and median peak thrombin generation were 66 nM (IQR 62, 87). Rivaroxaban 20 mg OD was safe and effective in a pilot study of 10 low risk patients with mechanical aortic heart valve. Our results justify larger studies investigating the application of anti-Xa inhibitors in patients with mechanical heart valves. Copyright © 2019. Published by Elsevier Ltd.