Hepatic veno-occlusive disease (VOD) is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). We evaluated in prospective analysis the usefulness of the pediatric EBMT criteria for VOD diagnosis and their presumable impact on cost effectiveness and patients' outcome. Study included all 282 HSCT procedures performed in Department of Pediatric Hematology/Oncology and BMT in Wrocław between January 2016 and March 2019. Data were compared with previous VOD research conducted in our center before year 2016. Twenty-five (8.9%) patients (median age 3.5 years) were diagnosed with VOD. Duration of defibrotide (DF) administration varied from 4 to 34 days (median: 16.5), with 96% response rate. Overall survival was 88%. If applying Baltimore and modified Seattle criteria, VOD incidence was 2.13% and 5.7%, respectively. Median diagnosis delay based on modified Seattle criteria was 3 days. Before 2016, VOD incidence was 4.9%, with 74% DF response rate (p = 0.033) and 56.2% OS (p = 0.008). After implementing new criteria length of hospitalization for VOD patients decreased by median of 12 days (p = 0.009). Earlier VOD diagnosis, facilitated by EBMT criteria, resulting in implementing immediate treatment significantly improved patients' outcome. Furthermore, it allows shortening of DF administration and minimizes length of hospital stay.