In a randomized, open-label, phase III study comparing the efficacy and safety of rivaroxaban and warfarin in patients with antiphospholipid syndrome (APS), rivaroxaban use was associated with an increased rate of adverse events. 120 patients with APS at high risk of thromboembolic recurrence were randomly assigned to receive either rivaroxaban (n = 59) or warfarin (n = 61), but the trial had to be stopped prematurely owing to safety concerns. In the rivaroxaban treatment group, adverse events occurred in 19% of patients (compared with 3% in the warfarin group), which included thromboembolic events (12% of patients) and major bleeding (7% of patients).