Regardless mass vaccination programs in Egypt with inactivated polyvalent vaccines of FMD virus. FMD virus is still persistent with major economic burden. Serotypes of FMD namely, A, O, and South African Territories (SAT2) are endemic with repeated outbreaks of new lineage. So, selection of appropriate vaccine is very difficult. In this study; Phylogenetic analysis of VP1 genome for the existing serotype (A, O and SAT2) between 2016 to 2019 approved circulation of serotype O of East Africa 3 (EA-3) topotype, AIran05 lineage and A Africa G-IV lineage of serotype A and topotype VII of serotype SAT2 including Alx-12 and Lib-12 lineages. Significant amino acid changes in critical antigenic sites between field isolates and vaccine strains were observed. The present findings indicate the importance of an active routine surveillance system incorporating antigenic and genetic analysis designated to continually update information about field isolates of FMDV. Such protocols may influence FMD control strategy in Egypt and surrounding country(s).