Introduction: A high risk of gastrointestinal bleeding has been reported with the use of some direct oral anticoagulants (DOACs). This risk may be of particular concern in individuals with associated anaemia. The aim of this study is to investigate potential differences in the risks of gastrointestinal bleeding and stroke among the four available DOACs in patients with atrial fibrillation (AF) and moderate or severe anaemia. Materials and methods: All Danish patients diagnosed with incident AF who had a baseline haemoglobin measurement and subsequently initiated DOAC therapy between 2012 and 2021 were identified through administrative registries. Only patients with moderate or severe anaemia (N = 7269) were included and evaluated regarding the risk of hospitalization for gastrointestinal bleeding and stroke. Standardized absolute 1-year risks of stroke and gastrointestinal bleeding were calculated from multivariable Cox regression analyses. DOACs were compared pairwise Results: Compared with apixaban, both dabigatran and rivaroxaban were associated with a significantly increased risk of gastrointestinal bleeding with standardized 1-year risk ratios of 1.73 (95 % confidence interval [CI], 1.10–2.35) and 1.56 (95 % CI, 1.18–1.93), respectively, while no significant difference was seen in the comparison of apixaban with edoxaban 1.32 (95 % CI, 0.41–2.32). No significant differences in gastrointestinal bleeding were observed with pairwise comparisons of dabigatran, rivaroxaban and edoxaban. Finally, no significant difference in stroke risk among the four DOACs was observed. Conclusion: In AF patients with moderate or severe anaemia, apixaban was associated with a significantly lower risk of gastrointestinal bleeding than dabigatran and rivaroxaban. No significant difference in stroke risk was observed across all four available DOACs.