Background: The Expanded Program on Immunization (EPI), initiated by WHO in 1974, is a cornerstone of public health. China’s EPI covers more than a sixth of the world’s population and includes eight routine vaccines with high coverage rates. This study aimed to estimate health and economic impacts of China’s EPI over the past 50 years (1974–2024). Methods: This study mathematically modelled the impact of all eight routine vaccines in China’s EPI against eight pathogens (measles, pertussis, hepatitis B, tuberculosis, hepatitis A, Japanese encephalitis, meningitis A, and poliomyelitis) based on data availability and their substantial disease burden, particularly accounting for non linearities in vaccine impact. Health and economic outcomes were determined using mathematical models between a counterfactual scenario without vaccination (vaccine coverage set to zero) and the current vaccination scenario (routine vaccination scheduled at age 0–6 years), based on calendar year and birth cohort approaches. The health impact of China’s EPI from 1974 to 2024 was measured in the number of cases, deaths, and disability-adjusted life years (DALYs) averted. Findings: We estimated that China’s EPI averted 703·02 million cases (95% credible interval 699·51–722·80) and 2·48 million deaths (2·14–2·97) in 1974–2024 based on the calendar year approach, equivalent to averting an estimated 160·22 million DALYs (145·05–196·99). Using the birth cohort approach, we predicted 707·41 million cases (703·93–727·03) and 7·01 million deaths (6·95–7·87) averted over the lifetime, corresponding to 279·02 million DALYs (265·78–316·12). From a societal perspective, the aggregated cost of vaccination was estimated to be US$124·06 billion (120·49–127·49), although the benefits amounted to $2417·85 billion (2359·38–2710·35). China’s EPI yielded an aggregate benefit–cost ratio of 19·48 (18·82–22·08) from the societal perspective and 8·02 (7·64–8·80) from the provider’s perspective. Interpretation: China’s EPI has shown remarkable health and economic achievements, contributing to worldwide EPI success in the past 50 years. Further investment in EPI is warranted to sustain coverage and expand vaccine inclusion in China and globally.