BACKGROUND Painful vaso-occlusive crises (VOC) are the most common reason for acute care utilization in patients with sickle cell disease (SCD), and the emergency department (ED) is often the site of initial management and treatment. Treatment guidelines recommend initiation of analgesia with parenteral opioids within 30 minutes of presentation, timely reassessment of pain, and additional opioids as needed every 15-30 minutes. These targets are infrequently met, resulting in uncontrolled pain, increased likelihood of hospital admission, and deterioration of physician-patient relationships. METHODS We undertook a multidisciplinary effort to improve the management of VOC in the ED, by development and implementation of an evidence-based clinical care pathway. The clinical pathway was implemented at the Hospital of the University of Pennsylvania in December 2018, with direct education of hematology and ED providers around the content of the clinical pathway, and availability of the pathway on the institutional intranet. Specific areas of focus in the pathway included appropriate triaging of patients as emergency severity index 2, timely administration of initial opioid dose, rapid reassessment and administration of additional opioid doses as needed, as well as appropriate laboratory evaluation and evaluation for other common and/or serious complications of SCD. Outcome measures included time from ED registration to administration of first opioid dose, time between administration of first opioid dose and second opioid dose, and proportion of patients discharged from the ED. Balance measures included rate of ED readmission and length of stay. RESULTS There were 602 ED visits from 103 unique patients in the study period, with 256 visits in the six-month period prior to pathway implementation and 346 visits in the six-month period after implementation. Following pathway implementation, time from registration to first opioid dose fell from 114 minutes to 93 minutes (p = 0.003). The proportion of patients receiving their first opioid dose within 60 minutes of registration increased from 19% to 33%. Time from administration of the first opioid dose to the second opioid dose improved from 117 minutes to 94 minutes (p = 0.002). The proportion of patients receiving their second opioid dose within 60 minutes of the first opioid dose increased from 27% to 37%. There was no change in the rate of hospital admission from the ED, or in the proportion of patients who left without being seen (p = 0.710). There was also no change in rate of ED readmissions (p = 0.138) or length of stay (p = 0.483). CONCLUSION Implementation of an evidence-based clinical care pathway in the ED for SCD patients presenting with VOC led to significant improvement in outcomes, with decreased time to first opioid dose and decreased time from first to second opioid dose. Nevertheless, very few patients received guideline-based care, particularly with the goal of time to first opioid dose of less than 30 minutes. While our data demonstrate that provider education and clinical pathways clearly improve the management of VOC in the ED, additional interventions will be required to target other barriers to optimal management, including implicit biases, negative provider attitudes, and social stigma surrounding SCD. Disclosures No relevant conflicts of interest to declare.