BackgroundOutbreaks of vaccine-preventable diseases continue to occur in low- and middle-income countries (LMICs), requiring outbreak response immunization (ORI) programs for containment. To inform future investment decisions, this study aimed to estimate the cases, deaths, disability-adjusted life years (DALYs), and societal economic costs averted by past ORI programs. Outbreaks of measles, Ebola, yellow fever, cholera, and meningococcal meningitis in LMICs between 2000-2023 were considered.Methods210 outbreaks (51 measles, 40 cholera, 88 yellow fever, 24 meningitis, 7 Ebola) were identified with sufficient data for analysis. Agent-based models were calibrated for each disease such that after controlling for baseline vaccine coverage, ORI initiation time, speed of vaccine delivery, environmental variables, or endemic prevalence of the disease, observed outbreaks were within the distribution of simulated outbreaks. A status-quo and no ORI scenario were compared for each outbreak.FindingsAcross 210 outbreaks, ORI programs are estimated to have averted 5·81M [95% uncertainty interval 5·75M–5·87M] cases (4·01M measles, 283K cholera, 1·50M yellow fever, 21·3K meningitis, 820 Ebola), 327K [317K–338K] deaths (20.0K measles, 5215 cholera, 300K yellow fever, 1599 meningitis, 381 Ebola), 14·6M [14·1M–15·1M] DALYs (1·27M measles, 220K cholera, 13·0M yellow fever, 113K meningitis, 16·6K Ebola), and US$31·7B [29·0B–34·9B] (US$710M measles, US$156M cholera, US$30·7B yellow fever, US$97·6M meningitis, US$6·72M Ebola) in societal economic costs. In general, the more rapidly the ORI was initiated the greater the impact.InterpretationORI programs are critical for reducing the health and economic impacts of outbreaks of vaccine-preventable diseases.FundingGavi,the Vaccine Alliance.