BACKGROUND: Efforts to ensure donor and recipient safety have reduced the population of eligible voluntary blood donors. The current method for determining eligible blood donors in a population using only age as the criterion for excluding donors poorly reflects the large constellation of factors known to cause donor deferrals. An epidemiologic model has been developed to determine the prevalence of donor exclusions and thus improve the estimate of total eligible blood donors in the nation. STUDY DESIGN AND METHODS: Epidemiologic databases were selected to enumerate the population prevalence of 31 donor exclusionary factors which correspond to the AABB standards. Prevalence data were adjusted for age, duration of exclusion, and comorbidities. This method yields the number of excluded individuals to calculate the number of eligible blood donors. RESULTS: The conventional method of calculating eligible donors indicates that there are approximately 177 million eligible blood donors in the US population. This study indicates that this method erroneously includes 66 million individuals who are ineligible due to known exclusionary factors. Only 111 million individuals in the US population are eligible to donate blood. CONCLUSION: The conventional method of determining eligible blood donors overestimates eligible donor prevalence by approximately 59 percent (111 million eligible individual blood donors rather than 177 million eligible individuals). It is recommended that a method similar to the one described in this study be utilized to additionally exclude potential donors not meeting AABB donation standards to improve accuracy of eligible blood donor estimations.