Background: Sickle-cell disease (SCD) causes significant morbidity, premature mortality, and high disease burden, resulting in frequent health care use. Comanagement may improve utilization and patient adherence with treatments such as Hydroxyurea. The purpose of this study was to describe acute-care utilization in Medicaid-enrolled patients with SCD, patient factors associated with comanagement, and adherence to Hydroxyurea.Methods: Data from 2790 patients diagnosed with SCD, age 1 to 65؉ years, enrolled at least 1 month in North Carolina Medicaid between March 2016 and February 2017, were analyzed. Outpatient visits were categorized as primary care, hematologist, and nonhematologist specialist. Nurse practitioners or physician assistants with unidentified specialty type or family practice were categorized separately. Comanagement was defined as a minimum of 1 primary care and 1 hematologist visit/patient during the study period.Results: There were notable age-related differences in utilization of health care services. Only 34.82% of the sample was comanaged. Comanagement was higher in the 1-to-9-year-old (44.88%) and 10-to-17-year-old groups (39.22%) versus the 31-to-45-year-old (30.26%) and 65؉-year-old (18.75%) age groups. Age had the greatest influence (AUC ‫؍‬ 0.599) on whether or not a patient was comanaged. Only a third of the sample (32.24%) had at least 1 Hydroxyurea (HU) prescription. Age was the most predictive factor of good HUadherence (AUC ‫؍‬ 0.6503). Prediction by comanagement was minimal with an AUC ‫؍‬ 0.5615.Conclusion : Comanagement was a factor in predicting HUadherence, but further studies are needed to identify the frequency and components of comanagement needed to increase adherence and reduce acute care utilization. (J Am Board Fam Med 2020;33:91-105.)Sickle-cell disease (SCD) is a genetic disorder and the most common rare blood disease in the United States. 1 Patients suffer from complications, includ-ing but not limited to stroke, acute chest syndrome, and severe painful crisis that contributes to morbidity and premature mortality. Individuals also suffer from significant disease burden, often resulting in a high number of hospitalizations, readmissions, emergency department (ED) visits, and other associated costs to the health care system. In 2006 people with SCD had an estimated 232,382 ED visits, 68,410 hospitalizations from the ED, accounting for an estimated $2.4 billion dollars. 2 In 2010, SCD was associated with the highest 30-day readmission rate (31.9%) among all diagnoses excluding cancer and cancer-related conditions. 3 Other national data representing about 1 ⁄3 of the SCD population found a similar 30-day readmis-This article was externally peer reviewed.