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Foot-and-mouth disease (FMD) continues to pose a significant threat in Egypt, necessitating thorough analyses of FMD virus (FMDV) outbreaks. This study analyzed 144 suspected FMD cases across 52 animal collections during the years 2017-2018 and 2022. Recurrent FMD outbreaks in vaccinated dairy cattle were investigated. Clinical observation, postmortem examination, and histopathological analysis were conducted. Samples were subjected to reverse transcription polymerase chain reaction (RT-PCR) using group-specific in addition to serotype-specific primers, along with direct gene sequencing of the VP1 gene from positive samples, followed by phylogenetic analysis. Signs, postmortem and histopathological lesions consistent with FMD were found. Molecular identification confirmed the presence of serotype A (G-IV topotype), O (O/EA3 topotype), and serotype SAT2 (SAT2/VII/Lib-03 topotype). All detected topotypes were distinct from currently available vaccine strains. Variations in amino acid in the epitopes of the structural protein VP1 were detected. The study highlights the genetic and antigenic variability of FMDV strains circulating in Egypt, indicating potential challenges for vaccine effectiveness., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)