Background and Aims: Hepatic veno-occlusive disease(VOD) is the serious complication after hematopoietic stem cell transplantation(HSCT) to cause significant morbidity and mortality. Defibrotide is used for treatment for VOD and the prophylactic role is under investigation now. Due to the cost and worry about the side effects, we investigated low dose defibrotide for prophylaxis Methods: Total 93 patients who received HSCT from March 2013 to July 2017 in Yonsei Cancer Center were reviewed retrospectively. We matched prophylaxis group (N=31) to non-prophylaxis group (N=62) by 1:2. Low dose prophylaxis was composed of half of usual dose and administered from D-3 to D+7. Results : Diagnosis in the cohort was medulloblastoma(29%), neuroblastoma(19%), primitive neuroectodermal tumor (15%), atypical teratoid rhabdoid tumor(11%), and others (26%). Median age at diagnosis was 4.0 (3.0 – 6.0) in prophylaxis group and 4.0 (3.0-6.0). Neutrophil engraftment was achieved at median 12.0 (11.0 – 13.0) days in prophylaxis group and 13.0 (12.0 – 14.0) in non-prophylaxis group. Median dose for prophylactic defibrotide was 13.0 (12.3-15.9)(mg/kg/day). In non-prophylaxis group, 9/62 (14.5%) developed VOD, whereas in prophylaxis group, only 1 in 31 (3.2%) developed VOD (p=0.098). In the first HSCT group, there was no VOD (0/14) in prophylaxis group compared with 4/44 (9%) developed VOD in non-prophylaxis group ( P=0.242). In the second HSCT group, 5.9% (1/17) in prophylaxis group developed VOD but 28% (5/18) developed in non prophylaxis group ( P=0.086). In total group, there was 9 transplant related mortality and 2 was related with VOD. VOD related mortality was in non-prophylaxis group. Conclusion: Low dose defibrotide prophylaxis was considered as effective for prevention of VOD related morbidity and mortality for HSCT.