Hospitalized patients with sickle cell disease (SCD) may use opioid medications for both acute and chronic pain management. Use of these medications may unintentionally generate diagnostic codes for opioid misuse including "opioid use," "opioid abuse," and "opioid dependence," which connote a behavioral problem or addiction. In this study, we sought to compare diagnostic codes for opioid misuse amongst hospitalized patients with and without SCD. We performed a cross-sectional study of hospitalized non-obstetric, non-surgical, and non-elective patients with SCD using the National Inpatient Sample published by the Agency for Healthcare Research and Quality Hospital Cost Utilization Project during years 2016-2019. We used descriptive statistics to characterize patient demographics and opioid misuse diagnostic codes. We used Chi Square testing to compare rates of diagnostic codes for opioid misuse between patients with and without SCD. There were 165 ± 3 hospitalizations for SCD per 100,000 US population. Patients with SCD had higher rates of opioid misuse diagnostic codes for "opioid use" (0.3% vs 0.1%,