Hematopoietic stem cell transplantation is a groundbreaking treatment that brings about a complete cure for intractable hematologic malignancy, including acute leukemia. Yet post-transplant recurrence and mortality due to post-transplant complications such as sinusoidal obstruction syndrome (SOS) and transplant-associated microangiopathy (TAM) are as high as ever. Further improvements to transplant methods are clearly needed. One means of reducing the post-transplant recurrence rate of the primary disease may be to strengthen the anti-cancer therapy and radiation therapy in the pre-transplant treatment. This approach brings a dilemma, however, because mortality increases due to transplant-related complications in connection to stronger treatment. The common origin for the occurrence of these complications is the presence of vascular endothelial dysfunction, a condition that often combines with the patient’s coagulopathy. After the transplant, we carefully monitor the blood coagulation test value in order to promptly ascertain any abnormalities. Next, we administer a new anticoagulant genetically recombined thrombomodulin drug that confers both anti-inflammatory action and endothelial protection actions. We are introducing this drug as an initiative to reduce mortality rates due to transplant-related complications.