Graft versus host disease (GVHD) remains a major cause of mortality and morbidity after matched unrelated hematopoietic stem cell transplantation (HSCT). Campath-1 H (alemtuzumab), a humanized monoclonal antibody to CD52 antigen, is thought to reduce GVHD incidence through in vivo T-cell depletion. Through the same mechanism it can potentially increase the risk of relapse by reducing the graft versus leukemia effect and possibly increase the risk of infection due to delayed immune recovery. A retrospective case analysis of 17 pediatric matched unrelated HSCTs done in our institution between January 2003 and June 2009 with Campath-1H as part of the pretransplant conditioning regimen was conducted. Grade I-II acute GVHD was noted in 29.4% of the HSCTs. No patient developed chronic GVHD. All but one patient with severe aplastic anemia engrafted. A relapse of primary disease was noted in 35.3% of the transplants. Three patient deaths were due to relapse and 1 due to disseminated varicella infection. Overall survival was 100% and 94% at 100 days and 1 year, respectively. Our experience suggests Campath-1H used as part of pretransplant conditioning regimen in pediatric unrelated HSCTs effectively reduces the risk of serious GVHD with no apparent increase in life-threatening infections or relapse compared with that reported with conventional regimens. Larger studies, with longer duration of follow-up, are required to further assess its role with regards to graft versus leukemia effect and to establish if the decreased incidence of GVHD and infectious complications is sustained in larger cohorts.