Sickle cell disease is an inherited disorder of the blood, and characterized by vasoocclusive crises (VOC), risks for pneumococcal infections and organ toxicities, is associated with morbidity and premature mortality. India, with a population of 1.2 billion individuals, is estimated to be home to over 50.0% of the world’s patients with sickle cell disease. The ßS gene [ß6(A3)Glu?Val; HBB: c.20A>T] has the highest prevalence in three socio-economically disadvantaged ethnic categories: the Scheduled Castes (SC), the Scheduled Tribes (ST), and Other Backward Class (OBC) groups in India. The tradition of endogamy practiced by the ethnic groups in India provides the rationale for the screening of individual populations to better understand the distribution of the ßS gene, guide counseling and awareness programs and aid development of public policy. We undertook a study to describe the prevalence of the ßS gene in these ethnic groups in the district of Nagpur, Maharashtra in Central India. Through community screening and subsequent targeted screening of high risk individuals, 35,636 individuals were screened, of whom 5466 were found to have sickle cell trait and 1010 were identified with sickle cell disease. Community screening revealed a sickle cell trait prevalence of 13.0% in the SC, 12.0% in the ST and 3.4% in the OBC population. This study describes the prevalence of the ßS gene within these groups in Central India determined by large scale community screening. This program has uncovered previously undiagnosed cases, provided detailed information to guide population-based disease counseling, prevention and comprehensive care programs.