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Pain in children with sickle cell disease (SCD) is the leading cause of acute care visits and hospitalizations. Pain episodes are a risk factor for the development of acute chest syndrome (ACS), contributing to morbidity and mortality in SCD. Few strategies exist to prevent this complication.We performed a before-and-after prospective multi-modal intervention. All children with SCD admitted for pain during the 2-year study period were eligible. The multi-modal intervention included standardized admission orders, monthly house staff education, and one-on-one patient and caregiver education.A total of 332 admissions for pain occurred during the study period; 159 before the intervention and 173 during the intervention. The ACS rate declined by 50% during the intervention period 25% (39 of 159) to 12% (21 of 173); P = 0.003. Time to ACS development increased from 0.8 days (0.03-5.2) to 1.7 days (0.03-5.8); P = 0.047. No significant difference was found in patient demographics, intravenous fluid amount administered, frequency of normal saline bolus administration, or cumulative opioid amount delivered in the first 24 hr. Patient controlled analgesia-use was more common after the intervention 52% (82 of 159) versus 73% (126 of 173; P = 0.0001) and fewer patients required changes in analgesic dosing within the first 24 hr after admission (26%, 42 of 159 vs. 16%, 28 of 173; P = 0.015).A multi-modal intervention to educate and subsequently change physician's behavior likely decreased the rate of ACS in the setting of a single teaching hospital. Pediatr Blood Cancer 2011;56:262-266. © 2010 Wiley-Liss, Inc.