OBJECTIVES: This study aimed to assess all-cause health care expenditures among persons with Sickle Cell Disease (SCD). METHODS: A retrospective cohort study was conducted using a multi-state Medicaid claims database. Inclusion criteria were being continuously enrolled in a covered health plan from January 1, 2012 through December 31, 2012 and diagnosis with SCD. SCD diagnosis was identified based on having at least one inpatient claim or at least two outpatient claims with ICD-9-CM codes for sickle cell thalassemia with or without crisis, or SCD with or without crisis. There was no explicit exclusion criterion. Mean expenditure and 95 percent confidence intervals (95% C.I.) were calculated for inpatient expenditures, outpatient expenditures, emergency room (ER) expenditures, long-term care expenditures, prescription drug expenditures, and total expenditures. Individuals with SCD and Sickle Cell Crisis (SCC) were identified based on having at least one claim with ICD-9-CM code for SCD crisis. Wilcoxon Mann-Whitney tests were used to assess difference in health care expenditures between groups. RESULTS: A total of 8,191 individuals met study SCD inclusion criteria, of which 4,716 (58%) had SCC. The mean (±standard deviation) age was 22.0 ± 17.1 years. A majority of the sample was female (54.4%) and most were African American (74.6%). Mean annual all-cause total health care expenditure was $16,486 (95% C.I.=$15,491 to $17,482). Individuals between 15 and 34 years old tended to have higher expenditures than comparatively younger or older patients. Compared to those without SCC, individuals with SCC had significantly higher mean annual total expenditures ($20,723 vs. $10,737, p<0.001), which was primarily due to higher inpatient expenditures ($11,908 vs. $2,152, p<0.001) and ER expenditures ($1,960 vs. $443, p<0.001). CONCLUSIONS: Sickle Cell Disease is associated with high health care expenditures. Individuals with SCD and SCC had much higher health care expenditures compared to those with SCD without SCC.