Background Many children with hematologic and oncologic diagnoses require opioids for management of pain, yet knowledge gaps persist among pediatric hematology/oncology (PHO) fellows. Objective Pediatric Opioid Analgesia Self‐Instruction System (PedOASIS) is an interactive, case‐based education tool designed for independent learning. The goal of this study was to evaluate its efficacy in increasing PHO fellows’ knowledge and comfort with using opioids to manage pain. Design/method PHO fellows were recruited from 74 American College of Graduate Medical Education‐accredited US programs during the 2019–2020 academic year and randomized to receive access to PedOASIS (intervention) or usual PHO training (control). Surveys at baseline, immediately after accessing the tool, and 6 months later assessed knowledge and comfort related to prescribing opioids. Results A total of 64 PHO fellows completed the study, with 32 in the intervention group and 32 controls. At baseline, mean scores on the 10‐question knowledge assessment were similar between groups (intervention: 5, control: 6; p = .8). Following intervention, mean score was significantly higher in the intervention group (9) versus controls (5; p < .0001). Six months later, scores in both groups decreased but remained significantly higher in the intervention group (7) compared to controls (5, p < .0001) and compared to baseline (p = .0002). Fellows in the intervention group reported significant increases in comfort dosing opioids after exposure to the tool (p = .02). Conclusion PHO fellows exposed to the tool had improved scores on validated knowledge questions and greater comfort using opioids for pain management compared to controls. We therefore suggest that PedOASIS warrants further evaluation as a potential tool for PHO fellows.