Background: Current estimates of blood group frequencies in Germany were often derived from studies involving less than 12,000 individuals. The frequency of the D category VI was unknown. Methods: ABO, Kell, and Rhesus blood group data of more than 600,000 donors were reviewed. Allele frequencies were derived by the maximum-likelihood method. The frequency of D category VI was determined in more than 70,000 Rhesus typings. Results: ABO allele frequencies were: O: 0.640, A: 0.279, B: 0.081. Rhesus haplotype frequencies were: cde: 0.394, CDe: 0.431, cDE: 0.136, cDe: 0.021, and Cde: 0.011. D category VI represented 7% of all weak D (formerly Du). The 95% confidence interval for the D category VI frequency was 1:3,600–1:11,200. Kell allele frequencies were: K: 0.040, and k: 0.960. 95% confidence intervals for rare phenotypes were: Oh: 1:88,000–1:1,760,000, p: 1:200,000–1:5,200,000, Rhnull: 1:180,000–1:10,300,000, and D-deletion: 1:180,000-0. Conclusions: We presented refined estimates of ABO, Rhesus D and Kell blood group frequencies and established reliable frequency estimates for Rhesus haplotype and some rare blood groups. The prevalence of D category VI was about 0.02%, which necessitates specific detection for Rh-D-negative transfusion therapy. A protocol is presented for Rh D typing in transfusion recipients, which obviates the need for an antiglobulin test.