Objective: To analyze the effect of implementing a comprehensive nursing management program for rabies vaccination patients. Methods: 100 cases of rabies vaccination patients were selected as observation objects from January 2022 to December 2023, and after enrollment, they were grouped according to the different nursing management programs, with 50 cases in each group. The control group was only given routine nursing management, and the observation group was combined with comprehensive nursing management on the basis of routine nursing management. The completion rate of vaccination, the rate of adverse reactions, and the satisfaction rate were assessed, comparing the clinical effects of different nursing management programs. Results: The completion rate of the 5th shot of rabies vaccination in the observation group was 82.00% higher than 64.00% in the control group (χ2 = 4.1096, P < 0.05); the rate of adverse reaction of vaccination in the observation group was 4.00% lower than 18.00% in the control group (χ2 = 5.0051, P < 0.05); the vaccination satisfaction in the observation group was 98.00% higher than 86.00% in the control group (χ2 = 4.8913, P < 0.05). Conclusion: The application of comprehensive nursing management program can help rabies vaccination patients to improve the completion rate of vaccination and reduce the incidence of adverse reactions to vaccination, with clear effects.