Over recent years, increasing recognition of venous thromboembolism (VTE) as a serious complication in hospitalized children and those with chronic medical conditions has highlighted the need for tailored prevention strategies across the pediatric age spectrum. The ASH ISTH Guidelines on Anticoagulant Prophylaxis for Pediatric Patients at Risk of VTE provide evidence-based recommendations to guide clinicians in using anticoagulant prophylaxis safely and effectively in newborns through adolescents, recognizing that pediatric thrombosis and bleeding risks differ markedly from adults and vary among subgroups. Grounded in the principle of “first do no harm,” these guidelines emphasize careful risk stratification, avoidance of prophylaxis in children at high risk of bleeding, and the development of institution-specific protocols to support consistent, high-quality peri-procedural and inpatient VTE prevention, while also identifying key gaps where further research is urgently needed.