To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days, and mortality rates were evaluated at 28 days. In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.