We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received Tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range 22-76). All patients received busulfan-based conditioning, and were transplanted with HLA-matched related or matched unrelated bone marrow or peripheral stem cell grafts. The median follow up for surviving patients was 15 months (range 9-20). The cumulative incidences of grades II-IV and III-IV acute graft versus host disease were 14% (95% CI 5-30) and 3% (95% CI 0-11) at day 100, and 17% (95% CI 7-31) and 6% (95% CI 1-16) at day 180, respectively. There was no difference in grades II-IV acute graft versus host disease in recipients that received myeloablative or reduced intensity conditioning regimens. Notably, there were no cases of graft versus host disease of the lower gastrointestinal tract within the first 100 days. A comparison to 130 matched controls who only received tacrolimus and methotrexate demonstrated a lower cumulative incidence of grades II-IV acute graft versus host disease (17% versus 45%, p=0.003) and a significant increase in grades II-IV acute graft versus host disease -free survival at 6 months (69% versus 42%, p=0.001) with Tocilizumab, tacrolimus and methotrexate which was the primary endpoint of the study. Immune reconstitution was preserved in patients treated with Tocilizumab, tacrolimus and methotrexate as T and B cell subsets recovered to near normal levels by 6-12 months post transplantation. We conclude that Tocilizumab has promising activity in preventing acute graft versus host disease, particularly in the lower gastrointestinal tract, and warrants further examination in a randomized setting.