Many Aeromonas species are infecting striped catfish in the Mekong Delta in Vietnam. This study aimed to evaluate the effectiveness of autogenous vaccines developed by analysing the genetic diversity through DNA fingerprint analysis. A total of 38 Aeromonas strains isolated from 2017 to 2022 were analysed for phenotypic differences using the repetitive element sequence PCR (rep-PCR) with the (GTG)5 single-primer. The vaccines were water-in-oil emulsion whole-cell inactivated with two monovalent vaccines containing antigens of Aeromonas VH31 (VC-VH31), or Aeromonas VH74 (VC-VH74) and a bivalent vaccine with both Aeromonas VH31 and VH74 (VC-VH31/74). The experiment lasted for 60 days in water at 28 °C and was performed in triplicates. Blood samples were taken at 0, 15, 30, 45 and 60 day post vaccination (dpv) to collect the serum. The challenge infection was performed as a co-infection immersion challenge of two homologous strains of Aeromonas VH31 and Aeromonas VH74 at dose LD60 value 0,55 × 107 cfu/mL and 0,47 × 108 cfu/mL, respectively. The highest relative percent of survival (RPS) of the VC-VH31/74 bivalent vaccine was 100 % and the fish displayed no clinical signs of disease. At 30 dpv, the concentration of total leukocytes, lymphocytes, monocytes and granulocytes was highest in the group receiving the dual vaccine. Additionally, the results showed that the difference between the vaccines was significant when ELISA analysis of IgM-specific antibodies in serum, and the result was highest in VC-VH31/74 bivalent vaccine after 30 days (p < 0.05) and remained stable until 60 dpv. The vaccine showed good immunogenicity and high protective efficacy against Aeromonas spp. in catfish. Thereby demonstrating the potential of Aeromonas autogenous vaccine use.