Protein S (PS) deficiency is widely recognized for its connection to venous thromboembolism risk. However, the relation between PS deficiency and arterial thrombotic events (ATEs) remains uncertain. Here, we report a patient who experienced an ATE with a family history of PS deficiency. We highlight an attention to the issues related to the management of arterial thrombotic events and discuss the potential use of antiplatelet therapy as a treatment option for a specific group of patients diagnosed with PS deficiency.