Background Worldwide, Sickle Cell Disease (SCD) is the most common monogenetic disorder. SCD is costly to the American health care system: $460,151 per patient for the 100,000 affected US patients. Biological and behavioral health comorbidities with limited hospital resources contributed to a cost increase in SCD readmissions at the Virginia Commonwealth University Health System (VCUHS) from 2012-2016, after a long history of decline. With increasing census, in FY16 the 30-day SCD readmission rate was 33.7%, up from 22.5% in FY14. The average SCD length of stay was 6.7 days, compared with an expected length of 4.2 days. The number of ED visits for SCD patients in FY17 was projected to be double that of FY14. The percent of ED returns in 3 days was projected to be triple that of FY14. Method The VCU Adult SCD Medical Home (ASCMH) was funded and launched to address this issue, based on the success of a pilot that showed cost savings of $333,000 for 5 patients in 12 months. The SCD ASCMH officially began January 1,2018 with a two-year pilot funding period. The ASCMH was structured and designed using quality improvement (QI) principles and consisted of multidisciplinary teams to coordinate inpatient care, emergency care, and ambulatory care respectively. Evaluation compared utilization during CY 2017 (pre-intervention) versus CY 2019 (2 years post intervention). For all patients we compared the average 30-day readmission rate, the average length of stay (ALOS), the average 3-Day ED return rate, the number of ED discharges, the numbers of inpatient days, inpatient discharges, and outpatient visits, the number of patients who used the ED, and total VCU charges. Results Among 541 (2017) and 592 (2019) SCD adults, including 40.6% males and 59.4% females, comparing pre-intervention to intervention, average utilization and VCU charges were either numerically or statistically significantly reduced. Mean 30-day readmission rates were reduced (31.60% vs 20.40%) ALOS was reduced (5.6 days vs 4.3 days), inpatient days were reduced (5313 days vs 3340 days), and total charges were significantly reduced ($15,664,895 vs $13,939,842). Conclusion At VCU, a multi-disciplinary ASCMH that featured intensive case management (CM) reduced annual utilization and cost savings for adult SCD patients. CM program elements that were most effective should be studied in the future and next steps should include a randomized controlled trial that can demonstrate evidence of their efficacy in strengthening and improving utilization Table Disclosures Smith: Emmaeus Pharmaceuticals, Inc.: Consultancy; GlycoMimetics, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; Imara: Research Funding; Novo Nordisk: Consultancy; Ironwood: Consultancy; Pfizer: Consultancy; Incyte: Other: Investigator; Health Resources and Services Administration: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire: Research Funding.