Riemerella anatipestifer infections impose significant economic burdens on duck production globally. Addressing the challenges posed by diverse serotypes, limited cross-protection, and varying field outbreaks, this study aimed to evaluate the safety, efficacy, and immunogenicity of three inactivated R. anatipestifer (R.A.) vaccines adjuvanted with montanide ISA70 oil, paraffin oil, and Salmonella Typhimurium lipopolysaccharide (S. Typhimurium LPS). The vaccines were administered to ducks, and their immune responses were assessed. The cellular immune response was measured through nitric oxide levels, while the humoral immune response was evaluated using the indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA). Challenge tests were conducted against virulent R.A. strains to determine protection percentages. The results indicated that the S. Typhimurium LPS-adjuvanted vaccine elicited the highest nitric oxide levels (150.23 μmol/mL), IHA titers (550), and ELISA levels (2.9 g/dL). This group demonstrated 100% protection postchallenge, while the montanide ISA70 oil and paraffin oil-adjuvanted vaccines showed 95% and 85% protection, respectively. Clinical signs and postmortem lesions were markedly reduced in vaccinated groups compared to the control positive group. The study underscores the potential of the S. Typhimurium LPS-adjuvanted R.A. vaccine in inducing robust immune responses and conferring significant protection against prevalent serotypes 1 and 2. This research offers insights into improving duck septicemia control strategies and emphasizes the importance of tailored vaccine formulations for enhanced protection against R. anatipestifer infections in duck populations.