In this study, we confirm the presence of FMDV three serotypes (A, O, SAT2) circulating in the Egyptian governorates and indicate the prevalence of the newly emerged FMDV. Also, we study the molecular characterization of the virus and epidemiological relationship between viruses of the same serotype to detect trans boundary FMDV movements that reveals the circulation of different serotypes and topotypes in Egypt (O-EA3, A- Iran-05 and SAT2- VII topotypes). Nucleotide sequence of the Vp1 gene and phylogenetic analysis confirmed the presence of Topotype O- EA-3 (East Africa-3) that was closely related to the recent Egyptian isolates but has high nucleotide divergence from the vaccinal strain used by 15% nucleotide difference, So, there is a need to investigate the cross protection between detected strains and the currently used vaccine to ensure maximum protection against the disease and the circulating virus and further studies on the immunogenic relationship and antigenic characters between the FMDV serotypes and the vaccine strain used for disease control with continuous follow up to the serotypes nucleotide sequence variability.