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Myocardial infarction (MI) is closely related to the Wnt signalling pathway, but the role of XAV939 (a Wnt/β-catenin signalling pathway blocker) in MI has not been elucidated. The purpose of this study was to explore the role of XAV939 in mouse hearts and to provide a new and feasible treatment for improving the prognosis of MI. C57BL/6 (male, 8 weeks old, 20-25 g) mice were selected for our study. The MI model was made by ligating the left anterior descending coronary artery. On day 28 after the operation, cardiac function was examined by echocardiography. Infarct size, fibrosis, and angiogenesis were individually measured by TTC assays, Masson's trichrome staining, and CD31 analysis, respectively. Apoptosis was examined by TdT-mediated dUTP nick-end labelling (TUNEL) staining. The expression of Wnt, β-catenin, caspase 3, Bax, and Bcl-2 was determined by western blotting. XAV939 successfully blocked Wnt/β-catenin signalling pathway activation in cardiomyocytes after MI by promoting the degradation of β-catenin. XAV939 suppressed fibrosis and apoptosis, promoted angiogenesis, reduced myocardial infarct size and improved cardiac function after MI. XAV939 can reduce myocardial infarct size and improve cardiac function by blocking the Wnt/β-catenin signalling pathway, which may provide a new strategy for improving the prognosis of MI., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)