Background: On December 14, 3 unvaccinated siblings with recent international travel presented to Children’s Hospital Colorado emergency department (CHCO-ED) with fever, rash, conjunctivitis, coryza, and cough. Measles was immediately suspected; respiratory masks were placed on the patients before they entered an airborne isolation room, and public health officials (PH) were promptly notified. Notably, on December 12, 1 ill sibling presented to CHCO-ED with fever only. We conducted an investigation to confirm measles, to determine susceptibility of potentially exposed ED contacts and healthcare workers (HCWs), and to implement infection prevention measures to prevent secondary cases. Methods: Measles was confirmed using polymerase chain reaction testing. Through medical record review and CHCO-ED unit-leader interviews, we identified patients and HCWs in overlapping ED areas with the first sibling, until 2 hours after discharge. Measles susceptibility was assessed through interviews with adults accompanying pediatric patients and HCW immunity record reviews. Potentially exposed persons were classified as immune (≥1 documented measles-mumps-rubella (MMR) vaccination or serologic evidence of immunity), unconfirmed immune (self-reported MMR or childhood vaccination without documentation), or susceptible (no MMR vaccine history or age <12 months). Susceptibility status directed disease control intervention, and contact follow-up was 21 days. Results: On December 14, all 3 siblings (ages 8–11 years) had laboratory-confirmed measles and were hospitalized. CHCO’s rapid isolation of the 3 cases within 5 minutes after presentation to the ED eliminated the need for exposure assessment on the day of hospitalization. However on December 12, the 1 ill sibling potentially exposed 258 ED contacts (90 patients, 168 accompanying adults) and 22 HCWs. The PH department identified 158 immune contacts (61%), 75 unconfirmed immune contacts (29%), and 19 susceptible contacts (8%); 6 contacts (2%) were lost to follow-up. Overall, 15 susceptible contacts received immune globulin (IG) postexposure prophylaxis and 4 contacts were placed on 21-day quarantine. Unconfirmed immune contacts self-monitored for measles symptoms and were contacted weekly by PH for 21 days. Moreover, 20 immune HCWs monitored symptoms daily; 2 susceptible HCWs were placed on 21-day quarantine. No secondary cases were identified. Conclusions: Rapid measles identification and isolation, high levels (90%) of immunity among contacts, prompt administration of IG, and effective collaboration between PH and CHCO prevented transmission.Funding: NoneDisclosures: None