Blood centers rely heavily on adolescent donors to meet blood demand, but presyncope and syncope are more frequent in younger donors. Studies have suggested administration of water before donation may reduce syncope and/or presyncope in this group.We conducted a randomized, controlled trial to establish the effect of preloading with 500 mL of water on the rate of syncope and presyncope in adolescent donors. School collection sites in Eastern Cape Province of South Africa were randomized to receive water or not. Incidence of syncope and presyncope was compared between randomization groups using multivariable logistic regression.Of 2464 study participants, 1337 received water and 1127 did not; groups differed slightly by sex and race. Syncope or presyncope was seen in 23 (1.7%) of the treatment and 18 (1.6%) of the control arm subjects. After adjusting for race, sex, age, and donation history, there was no difference in outcome between the water versus no water arms (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.42-1.53). Black donors had sevenfold lower odds of syncope or presyncope than their white counterparts (adjusted OR, 0.14; 95% CI, 0.04-0.47).Preloading adolescent donors with 500 mL of water did not have a major effect in reducing syncope and presyncope in South African adolescent donors. Our adolescent donors had lower overall syncope and presyncope rates than similar populations in the United States, limiting the statistical power of the study. We confirmed much lower rates of syncope and presyncope among young black donors.