In growing children, craniospinal irradiation (CSI) has historically treated the entire vertebral body (VB) to avoid potential long-term spinal abnormalities. Vertebral body-sparing proton craniospinal irradiation (VBSpCSI) is a technique that spares the majority of the VB from significant irradiation, and long-term safety outcomes have been reported previously. This retrospective study reviews the acute toxicity profile of children treated with VBSpCSI in a cohort comparison with photon-based craniospinal radiotherapy (3DCRT). Thirty-eight pediatric CSI patients treated between 2008 and 2018 were retrospectively evaluated for treatment-related toxicity. Acute toxicity outcomes and acute hematologic profiles were compared according to treatment modality, either VBSpCSI or 3DCRT. Statistical analysis was performed using Fisher's exact test for toxicity. Twenty-five patients received VBSpCSI and 13 patients received photon CSI. Mean patient age at treatment was 7.5years (range 2-16). The cohorts were well matched with respect to gender, age, and CSI dose. Patients receiving VBSpCSI had lower rates of grade 2+ gastrointestinal (GI) toxicity (24% vs. 76.5%, p=.005), grade 2+ nausea (24% vs. 61.5%, p=.035), and any-grade esophagitis (0% vs. 38%, p=.0026). Patients treated with VBSpCSI had lower red blood cell transfusion rates (21.7% vs. 60%, p=.049) and grade 4+ lymphopenia (33.3% vs. 77.8%, p=.046). VBSpCSI in children is a volumetric de-escalation from traditional volumes, which irradiate the entire VB to full or intermediate doses. In our study, VBSpCSI was associated with lower rates of acute GI and hematologic toxicities. Long-term growth outcomes and disease control outcomes are needed for this technique.