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<jats:p> Background: The time period after a pediatric hematopoietic stem cell transplant (P-HSCT) is tenuous as the patient is severely immunocompromised and awaiting immune reconstitution. Managing activities of daily living and medication administration after discharge from the hospital requires 24-hour care placing a heavy burden on caregivers and patients. Patients who do not adhere to the posttransplant regimen are at a higher risk for hospital readmission within the first 30 days of initial discharge with serious potential for life-threatening complications. The objective of this project was to improve 30-day readmission rates and caregiver readiness for discharge through the implementation of an evidence-based discharge protocol for P-HSCT patients and caregivers. Methods: This quality improvement project included development and implementation of comprehensive Pediatric Blood &amp; Marrow Transplant Guidelines and discharge protocol for patients who received an inpatient autologous or allogeneic HSCT and were scheduled for discharge from a 16-bed inpatient pediatric hematology–oncology unit of a children's hospital in the southeastern United States. Readmission rates were captured through the hospital-monitored system. Results: The comprehensive discharge protocol was implemented for six patients, and 30-day readmission rates decreased from 27.29% to 3.57% following the intervention. Discussion: Results suggest the combination of an evidence-based discharge protocol with a focus on caregiver readiness for discharge and a 24-hour Rooming-In period can influence caregiver confidence and reduce 30-day readmission rates after initial discharge from a P-HSCT. </jats:p>