Objective To discuss the curative effect and outcome of the Rh incompatiable allogeneic hematopoietic stem cell transplantation in the treatment of severe aplastic anemia (SAA). Methods One patient with SAA ages 46 (Rh negative) was enrolled in this study in our center on February 7th 2014. The donor is the brother of this patient, with matched HLA and Rh positive blood type. The patient was transplanted with allogeniec hematopoietic stem cell, and the conditioning procedure included fludarabine (FLU), cyclophosphamide (CTX) and rabbit anti-human T-lymphocyte immunoglobulin (ATG). Therapeutic effect of transplantation was reported with its relevant literature reviewed. Results Day 6 after transplantation patient began fever and was diagnosed with klebsiella pneumoniae septicemia. The body temperature returned to normal after therapy. The time of neutrophil and platelet recovery was day 17. The chimeric of bone marrow was 98.3%. Constantly low hemoglobin was treated with infusion and erythropoietin. The red blood cell in bone marrow was proliferated activity on day 31, and the hemoglobin returned to normal gradually. No hemolysis, and the patient received the Rh negative plasma-reduced blood 9 units and platelet 3 units. Up to now we followed this patient for 15 months. The blood and bone marrow were normal, and the chimeric status was 100%, no graft-versus-host disease and other complications occurred. Conclusions Transplantation with Rh incompatiable allogeneic hematopoietic stem cell in treatment of SAA is a safe and effective treatment modality.