To reveal the drug-resistance potential of Aeromonas hydrophila, the micro broth dilution method and comparative genomics method were used to analyze its drug-resistance potential in this study. The results showed that enrofloxacin, neomycin sulfate, florfenicol and doxycycline hydrochloride had inhibitory effects on the three strains, while sulfamethoxam had no inhibitory effect on the three strains. The resistance phenotype of the strains was not corresponding to the resistance genes one by one, and some strains could show related resistance phenotype even though the resistance genes were not annotated； The genomes of the three newly sequenced strains differed in size, and their genetic relationships were not close, but the number of drug-resistant genes was basically the same. After calculation of ANI （Average nucleotide identity）, comparative analysis of genomes revealed that the genomes of A. hydrophila showed strong variability, and there were still large differences among genomes of even close strains. Phylogenetic analysis showed that the strains from different hosts were scattered in the evolutionary tree, and the related strains were distributed in different countries and regions. A total of 21 drug resistance genes were annotated in all strains in CARD （The Comprehensive Antibiotic Resistance Database ）, of which 7 were shared by all strains. The reason for this phenomenon is likely to be due to the strong variability of A. hydrophila genome and the wide distribution of its hosts. Frequent gene exchange between strains promotes the rapid spread of drug-resistance genes throughout the species, so even if the genome changes between strains are large, the changes of drug-resistance genes between strains are small.