Background: An adequate blood supply depends on volunteer non-remunerated blood donors. African Americans have lower blood donation rates than whites. To improve African American blood donation rates, the motivators and barriers to African Americans must be explored. To study the differences in motivators and barriers to blood donation between donor and non-donor African American college students. Methods: African Americans college students at two Historically Black Colleges and Universities completed a 41-item, self-administered questionnaire, which assessed participant’s donation frequency, motivators and barriers toward donation, and knowledge and beliefs towards blood donation. Results: 364 primarily female college students (96% African Americans, 93% female) completed the questionnaire. 49% reported prior blood donation experience (donors) and 51% were non-donors. The primary motivator for donors and non-donors was convenience (89% donor, 82% non-donor). Donors were more likely than non-donors to disagree with statements regarding blood donation as being too painful (82% donor, 44% non-donor), resulting in feeling faint, dizzy, or nauseated (61% donor, 29% non-donor). Donors more often agreed that the blood supply is safe (77% donor, 58% non-donor), less often concerned about receiving a transfusion (61% donor, 73% non-donor), and more often aware of local blood shortages (50% donor, 35% non-donor). Conclusions: African Americans female college students are willing to donate blood given convenience and support from their university. Educational campaigns to increase knowledge regarding the safety of the blood donation process and the ongoing needs of an adequate blood supply might be effective methods to increase blood donation.