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Background and Objectives Materials and Methods Results Conclusion Some blood operators routinely screen blood donations for high‐titre (HT) anti‐A/B to reduce the risk of a haemolytic transfusion reaction due to out‐of‐group plasma‐rich components. We assessed donor factors associated with an increased likelihood of screening positive and compared routine data between England and Australia.Data were assessed from HT screening during 2018–2020 in Australia and 2018–2021 in England, totalling nearly 6 million blood donations. Screening was performed using a Beckman Coulter PK7300 analyser with a micro‐titre plate saline direct agglutination test in both countries, although different reagent red cells were chosen. HT‐positive was defined as testing positive at a titre of 128 or above.The likelihood of a donor testing HT‐positive was greater for females than males, declined with age and was dependent on the ABO group. However, the proportion of donors testing HT‐positive was consistently higher in Australia than in England: overall, 14% of group O donations and 5% of group A donations in England tested HT‐positive, compared with 51% and 22%, respectively in Australia. English data also showed that donors from Black, Asian or mixed ethnic backgrounds were more likely to test HT‐positive than White donors.These data demonstrate that donor sex, age, ABO group and ethnicity affect the likelihood of testing HT‐positive. Differences in testing methods likely had a significant impact on the proportion of donors testing as HT‐positive or ‐negative rather than any differences in donor populations. [ABSTRACT FROM AUTHOR]