Post-transplant cyclophosphamide (PTCy) has become the most popular approach in haplo-identical hematopoietic cell transplant (haplo-HCT). Although there are reports of a small number of adult patients in the literature who experienced graft failure and were re-transplanted with a haploidentical donor with PTCy prophylaxis, there is still insufficient guidance for patients with specific contraindications/complications to cyclophosphamide and virtually no data in the pediatric setting. Abatacept (Aba), a T cell co-stimulation blockade, has been shown in previous studies to prevent severe acute graft-versus-host disease (GVHD) with minimal toxicity and durable engraftment. We report the efficacy of Aba-based GVHD prophylaxis in four pediatrics patients (ages 2-12 years) who received a haplo-HCT with peripheral blood stem cells (PBSC). Three patients had previous transplants. One patient developed acute GVHD of skin stage 3 and one patient had both stage 3 skin and stage 1 GI acute GVHD. Two patients had mild chronic skin GVHD. All 4 patients are alive with full donor chimerism and without disease at 7-23 months follow up, weaning or off immunosuppressive agents with no complications. Successful haplo-HCT utilizing an Aba- based regimen can result in reliable engraftment and acceptable GVHD. However, our small sample size limits generalizability and encourages the consideration of a larger prospective trial to validate these results in the haplo-HCT setting.