Acute graft vs host disease (aGVHD) is a significant obstacle to successful allogeneic hematopoietic cell transplantation, as only 30-40% of those with aGVHD show complete response to front-line glucocorticoids. The role of mycophenolate mofetil (MMF) as salvage therapy in steroid-refractory aGVHD remains incompletely defined. Here, we examine outcomes of 27 patients with refractory aGVHD treated with MMF as second-line therapy. Seven (26%) patients achieved complete remission (CR) of steroid-refractory aGVHD with only the addition of MMF as salvage therapy. CR of aGVHD differed by overall grade at salvage (grade I, 1/3; grade II, 5/12; grade III 0/5; grade IV, 1/7) with odds ratio for CR in grade I/II vs III/IV of 7.3 (95% CI: 0.7-72.6, P=0.09). Overall survival (OS) at 3 years was 40%. Overall aGVHD grade at salvage (hazard ratio (HR) grade I/II vs III/IV 0.18 (95% CI: 0.06-0.57), P=0.003) and achievement of CR (HR 0.12 (95% CI: 0.04-0.39), P=0.0004) were significant predictors of OS. MMF was overall well tolerated, with only two patients requiring discontinuation for myelosuppression. MMF shows activity in the salvage of steroid-refractory, grades I-II aGVHD.