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Background: Despite potential benefits of medication therapy management (MTM) for complex pediatric patients, implementation of pediatric MTM services is rare., Objectives: To describe how a standardized pediatric MTM model identifies potential interventions and their impact on medication regimen complexity index (MRCI) scores in children with medical complexity (CMC) and polypharmacy., Methods: This retrospective proof-of-concept study included pediatric patients receiving primary care in a large outpatient primary care medical home for CMC within a tertiary freestanding children's hospital from August 2020 to July 2021. Medication profiles of established patients aged 0-18 years with at least 5 active medications at the time of the index visit were assessed for medication-related concerns, potential interventions, and potential impact of proposed interventions on MRCI scores., Results: Among 100 patients, an average of 3.4 ± 2.6 medication-related concerns was identified using the pediatric MTM model. Common medication-related concerns (>25% of patients) included inappropriate or unnecessary therapy, suboptimal therapy, undertreated symptom, adverse effect, clinically impactful drug-drug interaction, or duplication of therapy. A total of 97% had opportunities for 5.0 ± 2.9 potential interventions. Most common proposed interventions included drug discontinuation trial (69%), patient or caregiver education (55%), dosage form modification (51%), dose modification (49%), and frequency modification (46%). The mean baseline MRCI score was 32.6 (95% CI 29.3-35.8) among all patients. MRCI scores decreased by a mean of 4.9 (95% CI 3.8-5.9) after application of the theoretical interventions (P < 0.001). Mean potential score reduction was not significantly affected by patient age or number of complex chronic conditions. Potential impact of the proposed interventions on MRCI score was significantly greater in patients with higher baseline medication counts (P < 0.001)., Conclusion: Most CMC would likely benefit from a pharmacist-guided pediatric MTM service. A standardized review of active medication regimens identified multiple medication-related concerns and potential interventions for nearly all patients. Proposed medication interventions would significantly reduce medication regimen complexity as measured by MRCI. Further prospective evaluation of a pharmacist-guided pediatric MTM service is warranted., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)