OBJECTIVE: The study purpose was to compare medical appropriateness and costs of regional poison control center (RPCC) versus non-RPCC referrals to children's hospital emergency department (ED) for acute poison exposure. METHODS: This is a retrospective cross-sectional study of children (<6 years) during an 8-month period, who presented for poison exposure. Demographic and clinical patient characteristics were abstracted onto a uniform data form. Medical appropriateness was determined by presence of 1 of 4 criteria by 3 independent reviewers blinded to the patients' race, source of referral, charges, and disposition. RESULTS: Determination of medical appropriateness was matched by all 3 reviewers in 187 patients who make up the study population. There were 92 RPCC-referred cases and 95 non-RPCC-referred controls. Groups were comparable by age, sex, toxin, and symptoms. For RPCC referrals, 84 were self-transported, and 8 were transported by emergency medical services. For non-RPCC referrals, 60 were self-referred/transported, 26 were transported by emergency medical services, and 9 were physician referred. Regional poison control center referrals had a 39.1% higher rate of medical appropriateness than did non-RPCC referrals (odds ratio, 13.0; 95% confidence interval, 3.6-36.1). For this sample, mean charges for inappropriate ED poison exposure visits were $313.42, and the cost per RPCC call was $25, thus giving a potential return on investment of 12.54 to 1 favoring RPCC triage. CONCLUSIONS: When compared with other referral sources, RPCC triage results in fewer unnecessary ED visits in this age group. Increasing prehospital use of poison centers would likely decrease unnecessary ED referrals and related costs. Copyright © 2012 by Lippincott Williams & Wilkins.