Background: Despite an increasing incidence of venous thromboembolism (VTE) in pediatric patients in tertiary care settings, relatively few pediatric physicians have experience with antithrombotic interventions. Objective: These guidelines of the American Society of Hematology (ASH), based on the best available evidence, are intended to support patients, clinicians, and other health care professionals in their decisions about management of pediatric VTE. Methods: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews (up to April of 2017). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 30 recommendations, covering symptomatic and asymptomatic deep vein thrombosis, with specific focus on management of central venous access device–associated VTE. The panel also addressed renal and portal vein thrombosis, cerebral sino venous thrombosis, and homozygous protein C deficiency. Conclusions: Although the panel offered many recommendations, additional research is required. Priorities include understanding the natural history of asymptomatic thrombosis, determining subgroup boundaries that enable risk stratification of children for escalation of treatment, and appropriate study of newer anticoagulant agents in children.