The impact of thrombotic microangiopathy (TMA) on outcome was studied in 148 patients with acute graft-versus-host disease (GVHD) (> or =grade II). The Blood and Marrow Transplant Clinical Trials Network's definition for TMA was used to diagnose definite TMA. Probable TMA was diagnosed when none of the features of nephropathy and neurologic abnormalities associated with definite TMA were present. Overall, TMA developed in 43 (29%) patients; 16 definite and 27 probable. The occurrence of TMA, the maximum grade of acute GVHD and initial treatment failure were associated with shorter overall and GVHD-specific survival. The development of probable as well as definite TMA affected the survival of patients with acute GVHD adversely. These results show the clinical impact of TMA on patients with acute GVHD, and suggest that the proposed definitions and grading of TMA may need to be modified.