Data on direct oral anticoagulants (DOACs) in venous thrombotic antiphospholipid antibody syndrome (APS) are controversial. This pilot study aimed to assess the safety and efficacy of DOACs in APS patients requiring oral anticoagulation for venous thromboembolism (VTE) but unsuitable for treatment with vitamin K antagonists (VKAs). We performed a prospective multi-centre case-series including APS patients with previous VTE who were receiving treatment with DOACs due to ineligibility for VKAs. Main outcomes were bleeding, arterial and recurrent venous thrombotic events and all-cause death. We included 18 patients (median age 59.6 years, 66.7% women). The antiphospholipid antibody pattern was single positivity for 33.3% patients, double positivity for 33.3%, and triple positivity for 27.8%. Only one patient had seronegative APS. Apixaban, dabigatran, rivaroxaban and edoxaban were prescribed in 44.4%, 27.8%, 16.7% and 11.1% of patients, respectively. The mean follow-up was 50.1 ± 24.1 months. During the observation period, no recurrent VTE episodes or arterial thrombotic events were recorded. Four bleedings, of which 2 major, were reported. The incidence rate of bleeding was 5.3 per 100 patient-years (95% confidence interval [95%CI] 1.4-13.6). No intracranial bleedings were recorded.In conclusion, our preliminary findings may suggest DOAC as possible option for patients with venous thrombotic APS unsuitable to VKAs. Although these findings are promising, larger cohort studies are needed to confirm this finding.