The main aim of this study was to evaluate the impact of early T-cell chimerism status on the incidence and clinical course of acute graft-versus-host disease (aGVHD) in allogeneic transplant recipients after myeloablative conditioning. Of 62 patients, 38 (61%) had complete T-cell donor chimerism (DC), and 24 (39%) had mixed T-cell chimerism (MC). The incidence of early death (before day 100) with steroid-resistant aGVHD was significantly higher in patients with complete DC compared to patients with MC (6/38 vs. 0/24, p = 0.04). The time from aGVHD diagnosis to nonrelapse death was markedly different in patients with complete DC versus MC [53 days (range 12-183) vs. 238 days (range 135-550), p = 0.005]. Conditioning with Etopophos/total body irradiation (TBI) resulted in significantly more patients with MC compared to conditioning with cyclophosphamide/TBI. In conclusion, early complete T-cell DC was associated with a high incidence of early death in patients receiving high-dose steroids for the treatment of aGVHD.