Salmo trutta fario is one of the important cold-water economic fishes in Tibet. S. t. fario is delicious; contains no muscle spines; and is rich in amino acids, unsaturated fatty acids, and vitamins. It has become an important local high value-added aquaculture species. Diseases occur frequently in cultured S. t. fario,especially bacterial diseases such as gill rot and furuncle disease and fungal diseases such as saprolegniasis, which has caused huge economic losses to the S. t. fario farming industry. Therefore, disease research is of great significance to the large-scale healthy culture of S. t. fario. To determine the cause of death of S. t. fario, two dominant strains B1 and A3-2 were isolated from diseased S. t. fario and analyzed for virulence gene, animal regression infection, drug resistance gene, and drug sensitivity. The two dominant strains were identified as Aeromonas salmonicida B1 and Aeromonas sobria A3-2. A. salmonicida B1 showed strong pathogenicity to S. t. fario,while A. sobria A3-2 showed no pathogenicity to S. t. fario. Ten virulence genes were detected in A. salmonicida B1, including those of exotoxin (AerA, Act, and hly genes), extracellular enzyme (gcat, ahyB, and Lip genes), secretion system of III type (aexT, aopP, and ascF-G genes), and flagella (Fla gene). Five virulence genes were detected in A. sobria A3-2, including those of exotoxin (Act and Alt genes), exoenzyme (gcat genes), and secretory system III (aexT and aopP genes).A. salmonicida B1 was sensitive to 21 antibiotics, such as ceftriaxone, amoxicillin, florfenicol, ciprofloxacin, tetracycline, and streptomycin, and was only resistant to vancomycin. A. sobria A3-2 was sensitive to 17 antimicrobial drugs, such as ceftriaxone, florfenicol, ciprofloxacin, pipemidic acid, tetracycline, and streptomycin and was resistant to 6 antibiotics, including penicillin, amoxicillin, sulfisoxazole, trimethoprimsulbactam, and vancomycin. Three types of drug-resistant genes (AmpC, gyrA, and parC) were detected in A. salmonicida B1. Four types of drug-resistant genes (AmpC, gyrA, parC, and tetE) were detected in A. sobria A3-2. The drug-resistant genes detected in the two Aeromonas strains were basically consistent with the drug-resistant phenotype. A. salmonicida B1 was found to be an important pathogen causing fulminant death in S. t. fario. This study provides fundamental data on the infection characteristics of A. salmonicida, for vaccine development and disease prevention and control in the breeding process of S. t. fario.