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Background and aims We explored the role of ATP-binding cassette transporter A1 (Abca1), in post-myocardial infarction (MI) cardiac injury. Methods In Abca1–/– mice, wild type (WT) mice, and WT mice transplanted with Abca1–/– or WT bone marrow, an MI was induced in vivo. Furthermore, an ex vivo MI was induced in isolated Abca1–/– and WT hearts. Results Twenty-four hours and two weeks after in vivo MI induction, MI size was reduced in Abca1–/– (−58%, p = 0.007; −59%, p = 0.03) compared to WT. Ex vivo MI induction showed no effect of Abca1–/– on infarct size. Interestingly, two weeks after MI, Abca1–/– mice showed higher circulating levels of B-cells (+3.0 fold, p = 0.02) and T-cells (+4.2 fold, p = 0.002) compared to WT. Bone marrow-specific Abca1–/– tended to reduce infarct size (−43%, p = 0.12), suggesting a detrimental role for hematopoietic Abca1 after MI. Conclusions Although Abca1 has a protective role in atherosclerosis, it exerts detrimental effects on cardiac function after MI. Keywords