BACKGROUND: The consequences of temporary deferral are not well understood. This study sought to investigate blood donor return after deferral expiration. STUDY DESIGN AND METHODS: A retrospective cohort analysis of allogeneic whole-blood donation was conducted. All deferred donors and a random sample of eligible donors were identified from the year 2000, with subsequent blood center visits through December 2005 captured. Stratified results are reported as the percentage returning, rates of return, and time to return. Measures of statistical association and Cox regression modeling are reported. RESULTS: For first-time (FT) donors, 25 percent of temporarily deferred donors returned during the 5-year follow-up period compared to 47 percent of eligible donors (p < 0.0001); for repeat donors, 81 and 86 percent of deferred and eligible donors returned, respectively (p < 0.0001). Depending on the deferral category, 14 to 31 percent of FT and 58 to 90 percent of repeat donors returned. Rates (per year) of successful donation during the follow-up period were 0.09 for index-deferred FT donors, 0.28 for eligible FT donors, 1.0 for deferred repeat donors, and 1.45 for eligible repeat donors. Multivariate modeling indicated that in addition to deferral, age, sex, race, and education were associated with return in both FT and repeat donors. CONCLUSION: The effects of deferral were more pronounced than expected, affecting both FT and repeat donors. For FT donors, the type and duration of deferral, while important, were not as relevant as hypothesized because so few returned, suggesting the need to develop appropriate interventions to recapture those donors likely to be eligible.