Background: The emergence of multidrug-resistant Enterobacter aerogenes has become a public health concern. E. aerogenes is a common cause of hospital-acquired infections such as pneumonia and urinary tract infections. Aim: This study focused on the use of E. aerogenes ghosts as a potential vaccine against the opportunistic pathogen E. aerogenes. Methods: This study used a cost-effective method to generate the E. aerogenes ghosts using certain chemicals. The safety and effectiveness of the ghosts were evaluated in a mouse model by administering three doses over a 14-day period. The mice were then challenged with a live E. aerogenes strain. Results: The results of the cytokine assays showed that vaccinated mice produced higher amounts of IL-10 and TNF-α than did control saline mice, indicating a good immune response. Additionally, the results of the liver function tests indicated that there was a decrease in the activities of ALT and AST in the vaccinated mice as compared to the non-vaccinated mice and low levels of TP and Alb in non-vaccinated mice, suggesting a reduced liver injury and inflammation in vaccinated mice. Conclusion: Overall, the study suggests that E. aerogenes ghosts may be a promising candidate for use as a vaccine against E. aerogenes infection.