However, acquired Protein S deficiency occurs secondary to liver disorders, malignancy, pregnancy, nephrotic syndrome, and acute phase reactions.2 Protein S is principally synthesized in hepatocytes and ordinarily in megakaryocytes, osteoblasts, endothelial, Leydig, and vascular smooth muscle cells.3 The prevalence of protein S deficiency is 0.03-0.13% in Western countries.1 Here, we present a case of 40 years old male with protein S deficiency leading to chronic recurrent deep vein thrombosis (DVT) presenting with multiple episodes of post-thrombotic syndrome. The gene discussed is PROS1; the disease is hyperinsulinemic hypoglycemia, familial, 4.