Sickle-cell disease is not a reportable condition, making it difficult to ascertain the number of affected individuals. We estimated the number of people with sickle-cell disease for the United States and each individual state, adjusting for increased mortality. US Census population data for each of the 50 states plus the District of Columbia were obtained. The published prevalence of sickle-cell disease for blacks and Hispanics of either Mexican or non-Mexican ancestry was applied. Analysis revealed 89,079 (95% confidence interval: 88,494-89,664) people with sickle-cell disease in the United States, 80,151 black and 8928 Hispanic. The state with the highest sickle-cell population was New York with 8308, followed by Florida with 7539, and Texas with 6765 people with sickle-cell disease. This study provides important information for researchers and policymakers attempting to better plan for the care of the sickle-cell population. Sickle-cell disease is the most common inherited blood disorder in the United States. It is responsible for approximately 113,000 hospitalizations and $488 million dollars in hospitalization costs annually in the United States [1]. Although sickle-cell disease is a genetic disease diagnosed in this era by newborn screening, it is not a reportable condition. Therefore, it is difficult to ascertain the number of affected individuals in the United States. Newborn screening is an effective tool for diagnosis, but its use was not widespread until the late 1980s and 1990s [2], and it does not account for immigration. Further complicating population estimates is the increased mortality associated with the disease, both compared to the mortality for the underlying racial/ethnic group and when comparing more severe forms of the disease (hemoglobin SS (HgbSS) and hemoglobin S beta thalessemia (HgbSB 0)) to less severe forms of the disease (hemoglobin SC (HgbSC) and HgbSB 1) [3-7]. Recent advances such as prophylactic penicillin and vaccines have reduced mortality, but only for those young enough to have received the treatments [8,9]. While no published studies have estimated the prevalence of sickle-cell disease in the United States, one NIH estimate puts the number ''between 50,000 and 75,000;'' another at 80,000, and the Sickle Cell Disease Association of America estimates the number to be ''over 70,000'' [10-12] Methods Census level-data and prevalence. Census data by age and race/ethnicity were obtained for each individual state and the District of Columbia and summed to equal the United States as a whole [13]. Year 2005 was used as the baseline. The applied prevalence rate of sickle-cell disease for blacks was 289 per 100,000 live births [14]. Prevalence rates for Hispanics were 89.8 Hispanic children of non-Mexican ancestry per 100,000 live births and 3.14 Hispanic children of Mexican ancestry per 100,000 live births [14]. These prevalence rates were applied to the Hispanic population numbers in each state based on the state's ratio of the number of Mexican births to non-Mexican births, assum...