Objective: To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among severe septic patients with sepsis-induced disseminated intravascular coagulation (DIC) Design: Single-center, open-label, randomized controlled trial Setting: Single tertiary hospital Participant: 92 severe septic patients with sepsis-induced DIC Interventions: Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. Randomization was performed by the envelope method. The treatment group (rhTM group, n = 47) was intravenously treated with rhTM within 24 h of admission (day 0), and the control group (n = 45) did not receive any anti-coagulants, except in cases of deep venous thrombosis and pulmonary embolism. Primary and secondary measurements: Data were collected on days 0 (admission), 1, 2, 3, 5, 7, and 10. The primary outcome was survival at 28 and 90 days. The secondary endpoints comprised changes in DIC scores, platelet counts, D-dimer, antithrombin III (ATIII), and C-reactive protein (CRP) levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis. Main Results: The 28-day survival rates were 84 and 83% in the control and rhTM groups, respectively (p = 0.745, log rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p = 0.94, log rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p = 0.001, log rank test). Relative change from baseline of D-dimer levels were significantly lower in the rhTM group than in the control group, on day 3 and 5. Conclusion: rhTM treatment decreased D-dimer levels and facilitated DIC recovery in severe septic patients with sepsis-induced DIC. However, the treatment did not improve survival in this cohort.