Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m2per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m2per day, days 1 to 5; cycles 2 to 12: 200 mg/m2per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee-assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.