Studies have shown that postoperative disseminated intravascular coagulopathy (DIC) occurs in some patients with cardiac disease, acute aortic dissection, and ruptured abdominal aortic aneurysm. The specific pathophysiology of DIC in these settings are related to low cardiac function, shock, infection and sepsis as well as activation of coagulation cascade in the aneurysm sac or dissected aorta. A soluble form of recombinant human thrombomodulin (rhsTM) was approved in 2008 for the treatment of DIC. This report describes the safety and efficacy of rhsTM for the treatment of DIC in patients with cardiovascular disease operated in our department. Between October 2010 and March 2012, 35 patients with postoperative DIC were treated with rhsTM. Diagnosis of DIC was based on the diagnostic criteria for DIC of the Japanese Association for Acute Medicine (JAAM). During the first 6 months of the study period, after a diagnosis of DIC was made, the patients were treated with gabexate mesilate and antithrombin III, and if patients showed no improvement with conventional treatment, they received rhsTM for 6 days. During the last 10 months of the study period, patients received rhsTM soon after a diagnosis of DIC was made. Twenty seven patients survived for 28 days after rhsTM treatment, and the mortality rate was 22.9% (8/35). Patients who survived showed improvement in acute phase DIC scores, FDP levels, D-Dimer, fibrinogen and platelet counts during rhsTM treatment, but no improvement was observed in patients who died. No serious adverse events were found up to 28 days after the start of rhsTM administration. In conclusion, this study showed no adverse events of rhsTM, and further studies are needed to confirm that rhsTM administration is an effective therapeutic modality in the management of DIC after cardiovascular surgery.