OBJECTIVES: Sickle cell disease (SCD) is an inherited disorder predominantly affecting people of African descent, and is characterized by the production of defective hemoglobin. Patients with SCD may experience intermittent and sometimes life-threatening complications often leading to frequent hospitalizations. Hydroxyurea (HU) is the only pharmacologic intervention approved (in 1998) for the treatment of adult SCD. This study expands upon previous research (Lanzkron et al, 2006) and generates national estimates of changes in SCD-related hospitalization rates and associated resource use in the United States (US) following approval of HU. METHODS: Discharge data from the 1996-2005 HCUP Nationwide Inpatient Samples for adult (≥20 years) African American (AA) patients with a primary SCD diagnosis (ICD-9-CM codes 282.6, 282.6x) were analyzed. Weighted, age-standardized hospitalization rates, and estimates of total charges and length of stay (LOS) were calculated for the 2 years before (1996-1997) and 8 years (1998-2005) following approval of HU. RESULTS: The age-standardized rate of SCD-related hospitalizations (per 10,000 2008 US adult AA population) has fallen appreciably from just before HU’s approval in 1997 to 2005, from 17.3/10,000 to 13.8/10,000, a reduction of ~20%. During this period, the mean LOS has remained roughly unchanged (~6 days), though interestingly, mean total charges (in 2008 USD) incurred during an SCD-related stay have increased nearly 65%, from $15,197 in 1997 to $25,005 in 2005. CONCLUSIONS: We examined changes in rates of SCD-related hospitalizations and associated outcomes among AA patients following approval of HU for treatment of adult SCD. We observed a general decrease in the rate of  hospitalizations over the first 7 years following approval of HU. However, little difference in LOS was seen, and total charges for this patient group have increased appreciably for unknown reasons. Clinicians and other decision-makers should be aware of the impact that HU appears to have on SCD-related inpatient outcomes.