BACKGROUND: Blood transfusion therapy is an established treatment for primary and secondary prevention of strokes in children with sickle cell disease (SCD), a disease that predominantly affects African Americans. African American blood donors are more likely to have compatible minor red blood cell antigens for children with SCD who routinely receive transfusions. This study tested the hypothesis that when informed at church about the importance of blood donation, African Americans will have a higher than expected rate of first-time blood donation compared to the general population. STUDY DESIGN AND METHODS: The Sickle Cell Sabbath Program was developed to increase awareness about SCD and the importance of blood donations within the African American faith community. Church involvement in the program included a 5-minute scripted educational session about SCD that included the importance of blood donations followed by a blood donor drive that was hosted by the church. RESULTS: Thirteen African American churches sponsored 34 blood drives from 2003 through 2006. Each church sponsored at least two blood drives. Approximately 1200 donors participated in the sickle cell blood drives. The majority of the donors were first-time donors and represented a greater than expected first-time donor rate when compared to first-time donors in the metropolitan St Louis area, 60 percent (422 of 699) and 12.2 percent (21,516 of 175,818), respectively (p = 0.001). CONCLUSION: An educational program that engages the African American faith community more than quadruples the rate of expected first-time blood donors when compared to the general community over this 4-year period.