Hemorrhagic septicemia (HS) is an acute and highly contagious disease of water buffaloes and cattle. Financial losses due to HS made it an important disease. HS control is generally attained with subcutaneously injected killed vaccines. However, with some other de-merits, these vaccines provide only short-term protection and are difficult to administer. In present study, live aerosol vaccine was prepared using live Pasteurella multocida B:3,4 that was non-pathogenic strain and tested for efficacy in buffaloes and cattle. The live aerosol vaccine was prepared using 15% trehalose as stabilizer. Safety test of vaccine was conducted in calves. Each calf was administered 100 times the recommended dose of vaccine through intra-nasal route. The calves were kept under observation for 14 days. Vaccinated animals did not show any undesirable reactions. Body temperature remained normal. Food and water intake were as usual. Results suggestively exhibited the safety of the vaccine. For efficacy test, buffaloes and cattle were divided into two groups. The animals of one group were given live aerosol HS experimental vaccine at the dose of 1 ml/animal containing 2.7×10⁷ viable organisms through intra-nasal route. The animals of second group were injected with commercially available killed HS vaccine at the dose of 3 ml/animal through subcutaneous route. Protective anti-LPS-IHA antibody titer against P. multocida for live aerosol vaccine was detectable up to 12-month post vaccination while killed vaccine titer was detectable up to 6 months. Results revealed that the antibody levels in animals vaccinated with aerosol vaccine were significantly higher than killed vaccine. The efficacy of the vaccine was further evaluated using challenge protection test. Two groups of animals containing vaccinated and unvaccinated animals were challenged with 1 ml of the diluted broth culture containing 2×10⁷ viable organism of P. multocida B:2 that was pathogenic strain. Observation of both the groups for 14 days revealed that unvaccinated animals displayed signs of HS disease while animals of vaccinated group protected against the challenge. Results of challenge protection test confirmed the efficacy of live aerosol HS vaccine. It was concluded that the live aerosol vaccine conferred improved protective immunity against P. multocida B:2 infection and reduced frequency of the vaccination in buffaloes and cattle.