Edwardsiella tarda is a common fish pathogen, causing significant septicemic diseases in fish. This study was carried out to investigate prevalence of E. tarda among Tilapia zilli at EL manzla lake, Dakahlia governorate and characterize the isolates phenotypically and genotypically in addition to detection of multi-drug resistance genes (B-lactames genes and plasmid-mediated quinolone resistant genes by PCR assay. Therefore, (100) samples of Tilapia zilli collected from different localities. Fish samples were subjected to clinical and post-mortem examination then bacteriological examination from liver, kidney and spleen. The suspected isolates were characterized by cultural and morphological characters, some conventional biochemical tests and API 20E system then by PCR assay. Eighteen % isolates were characterized as E. tarda. Furthermore, detection of antimicrobial resistance genes by PCR, the recovered isolates harbored blaSHV and blaOXA-1 with a prevalence of 50% and 25%, respectively with no detection of aac (6′)-Ib-cr and qepA genes in examined isolates. The results of antibiotics sensitivity showed resistance to Nalidixic acid, Lincomycin, Amoxicillin and Norfloxacin and most of isolate were found to be sensitive to Florfenicol and Neomycin.55.6% of recovered isolates showed resistance to three antibiotic classes and 27.7% of recovered isolates showed resistance to four antibiotic classes and considered as MDR.  The emergence of MDR-strains represents a threat-alarm and PCR is very rapid method for identification of E. tarda isolates which may be helpful in control of Edwardsiellosis.