Background Discharge education practices vary among institutions and lack a standardized approach for newly diagnosed pediatric oncology patients and their parents. Objective The purpose of this American Nurses Credentialing Center–supported pediatric multisite trial was to determine the feasibility and effectiveness of 2 nurse-led Parent Education Discharge Support Strategies (PEDSS) for families with a child who is newly diagnosed with cancer. Interventions/Methods A cluster randomized clinical trial design assigned 16 Magnet-designated sites to a symptom management PEDSS intervention or parent support and coping PEDSS intervention. Outcome measures evaluated at baseline, 1, and 2 months after diagnosis include symptom experiences, parent perceptions of care, unplanned service utilization, and parent evaluation of the PEDSS interventions. Results There were 283 newly diagnosed children and their parent participating in this study. Linear mixed models revealed pain differed over time by the intervention; children in the symptom management group had a greater decrease in pain. Greater nausea and appetite disturbances were experienced by older children in both groups. Fatigue and sleep disturbance showed a significant decrease over time in both groups. The symptom management group reported significantly greater satisfaction with the PEDSS intervention. Conclusions This study is among the first to examine the effects of 2 different early-discharge planning strategies for families of a newly diagnosed child with cancer. The evidence supports a standardized discharge education strategy that can be successfully implemented across institutions. Implications for Practice Nurses play a major role in the educational preparation and discharge of newly diagnosed pediatric cancer patients and their families.