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Background: Asymptomatic blood donors can transmit human parvovirus B19 (B19V)., Methods: We assessed the B19V prevalence among a large cohort of blood donations collected in Germany during 2015-2018., Results: In total, 167 123 donations were screened for B19V deoxyribonucleic acid with 22 cases of viremia identified (0.013% positive). Infections peaked at a 4-year interval and the highest number of cases occurred in the summer months. All 22 infections were found in rhesus D-antigen-positive donations, suggesting a protective factor in donors who lack this antigen., Conclusions: These findings contribute to our understanding of risk factors for B19V infection among central European blood and plasma donors., Competing Interests: Potential conflicts of interest. U. F., M. E., L. B., H. H., T.-E. S., and R. G. are all employed at Octapharma, a company specialized in the development and production of human proteins from plasma and cell lines. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)