In South Africa, success in recruiting first-time African-origin blood donors at low risk for HIV infection has been tempered by lower-than-anticipated return rates. We studied whether self-reported motivators and deterrents could predict actual donor return among first-time donors. We administered a questionnaire on blood donation motivators and deterrents within 2 months after donation to a cohort of first-time African-origin blood donors in 2014 and followed their return behavior for 1 year. Survey responses associated with return within 1 year were assessed using separate multivariate logistic regression models for motivators and deterrents. A total of 2902 first-time African origin donors with median age of 23 years and female predominance (59%) were included. Within 1 year 1574 (54% of donors) attempted at least one additional donation. Donors were more likely to return if they strongly agreed with the statement "Blood donation is an easy way to make a difference" (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-2.9) and "I donated in response to advertisements on the radio, TV or newspaper" (OR, 1.6; 95% CI, 1.2-2.1). English language preference and nonstudent employment status were also associated with donor return. Poor customer service (OR, 0.45; 95% CI, 0.28-0.71), geographic region, and nonstudent employment status were associated with donor return in the deterrent model. Prosocial motivators and marketing communications predicted return, while poor customer experience predicted nonreturn. This novel design allowed us to study the link between donation motivators and deterrents and actual return for donation in the African context. © 2019 AABB.