Edwardsiella tarda, a pathogenic bacterium potentially lethal to fish, exhibits resistance to multiple antimicrobials, necessitating the regular monitoring of its antimicrobial susceptibility. Therefore, in this study, we aimed to characterize E. tarda strains, especially their antimicrobial resistance profiles, isolated from 15 different fish species in Brazil using phenotypic and genotypic approaches, and to establish a provisional epidemiological cutoff value. In total, 71 E. tarda strains were identified using mass spectrometric, multiplex-PCR or dnaJ gene sequencing. The isolates were subjected to disk diffusion test with multiple antimicrobials, and the provisional epidemiological cut-off was determined using the normalized resistance interpretation method. The isolates were examined for the presence of antimicrobial resistance genes (blaTEM, tetA, sul1, and floR) using PCR assays. Statistical analyses, including Fisher's exact test, Cramer's V coefficient, and multiple correspondence analysis, were conducted. Notably, 26.76, 26.76, 7.04, 18.30, 11.26, and 8.45 % of the isolates were classified as nonwild-type for oxytetracycline, norfloxacin, lincomycin-spectinomycin, amoxicillin, florfenicol, and trimethoprim-sulfamethoxazole, respectively. Additionally, 15.49 % of the isolates were multidrug-resistant. Multiple correspondence analysis revealed the susceptibility of Colossoma macropomum isolates to oxytetracycline and florfenicol and resistance of Oreochromis niloticus strains to the same drugs. Specifically, blaTEM, tetA, sul1, and floR resistance genes were detected in 39.43, 47.88, 11.26, and 19.71 % of the isolates, respectively. In conclusion, we assessed epidemiological cut-off values for E. tarda strains in Brazil. Some of the identified isolates contained specific resistance genes and were resistant to antimicrobials currently licensed (florfenicol and oxytetracycline) for use in Brazil. Overall, our findings highlight the serious health challenge posed by the potential transmission of antimicrobial-resistant strains in national aquaculture.