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Background and Objectives: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)