Background: To quantify the impact of vaccination on public health, we presented updated estimates of disease incidence with and without globally recommended pediatric immunizations. As of 2023, children under 10 in Cairo are routinely immunized against 14 vaccine-preventable diseases. Objective: This research aimed to study the effect of vaccination on the incidence of pediatric infectious diseases. Material and methods: We calculated the percentage decrease in overall and age-specific incidence for each condition after correcting for underreporting, as well as the annual number of cases prevented by vaccination by multiplying the incidence rates before and after the vaccine by the estimated population of Cairo in 2023. The incidence of prevaccine disease was either estimated using Cairo population estimates for the same era and annual case estimates from the prevaccine period, or it was derived from published statistics. The vaccine-era incidence was calculated using the average incidence during the last five years of available surveillance data or published estimates in the absence of surveillance data. Result: Routine immunization reduced the incidence of all targeted illnesses, with reductions ranging from 17% for influenza to 100% for diphtheria, Haemophilus influenzae type b, measles, mumps, polio, and rubella, resulting in over 24 million cases of vaccine-preventable disease avoided for Cairo's 328 million residents in 2023. The two diseases with the highest estimates of vaccine-era illness incidence were influenza (13,412 per 100,000) and acute otitis media caused by Streptococcus pneumoniae (2756 per 100,000). Conclusion: The incidence of all targeted diseases has significantly and sustainably decreased in Cairo as a result of systematic childhood vaccinations. Efforts must be undertaken to maintain and expand vaccination coverage in order to sustain low incidence levels of diseases that can be avoided by vaccination.