To study the possibility of differentiation between foot and mouth disease virus (FMDV) vaccinated and infected cattle, 100 cattle were used, 70 of them were non vaccinated while the remainder 30 were vaccinated against FMDV. These animals were examined clinically and investigated with two forms of enzyme linked immunosorbent assay (ELISA). The 1^st form (indirect sandwich ELISA) was used for detection and serotyping of FMDV while the 2^nd form (standard ELISA) was used to identify antibodies against non-structural proteins of FMDV (present in active FMDV that responsible for infection and absent in vaccination virus). Clinical examination showed that 14 cattle were suffered from salivation, lameness and rise of body temperature while the remainder of cattle were apparently healthy. By using indirect sandwich ELISA, three serotypes (O,A and C) of FMD virus were reported. Serotype O was detected in 16 non vaccinated and 21 vaccinated cattle, serotype A was detected in 7 non vaccinated cattle and serotype A was detected in 2 non vaccinated cattle. After performing standard ELISA five types of antibodies against FMDV non structural proteins (Lb, 2C, 3A, 3D and 3ABC) were recorded. All of these antibodies (except antibodies against non-structural protein Lb) were observed in 25 non vaccinated cattle while antibodies against non structural protein Lb were observed in 16 non vaccinated cattle only, all of these cattle w proved to be positive for FMDV by indirect sandwich ELISA. The study proved that there is no relation between FMDV serotype and presence of FMDV non structural protein as antibodies against non structural proteins were detected  in animal infected with any of three FMDV serotypes recorded in the study. Results of the present work proved that indirect sandwich ELISA could use in detection and typing of FMDV but could not use in differentiation between FMDV vaccinated and infected cattle as it gave positive results with both animals. At the same time, standard ELISA used successfully in differentiation between FMDV vaccinated and infected cattle and gave positive results with infected cattle only. Therefore, our study recommend using standard ELISA based on detection of any type of  antibodies against non structural proteins of FMDV (except non-structural protein Lb which recorded in some but not all infected animals) as it is sensitive technique in diagnosis of FMD even in apparently healthy animals and it is capable of differentiation between FMDV vaccinated and infected animals successfully. Differentiation between vaccinated and infected cattle is an important step in control of FMD in Egypt. This is the first study investigate differentiation between FMDV vaccinated and infected animal, the first to identify antibodies against non structural proteins of FMDV in Egypt and the first to study the relation between FMDV serotypes and presence of FMDV non structural proteins