SummaryBackgroundVaccine impact and cost-effectiveness models have mostly focused on acute burden.Shigella-attributable moderate-to-severe diarrhoea has been shown to be associated with childhood linear growth faltering. Evidence also links less severe diarrhoea to linear growth faltering. AsShigellavaccines are in late stages of clinical development, we aimed to estimate the potential impact and cost-effectiveness of vaccination againstShigellaburden that includes stunting and the acute burden attributable to less severe diarrhoea and moderate-to-severe diarrhoea.MethodsWe used a simulation model to estimateShigellaburden and potential vaccination in children aged 5 years or younger from 102 low-income to middle-income countries from 2025 to 2044. Our model included stunting associated withShigella-related moderate-to-severe diarrhoea and less severe diarrhoea and we explored vaccination impact on health and economic outcomes.FindingsWe estimate 109 million (95% uncertainty interval [UI] 39−204)Shigella-attributable stunting cases and 1·4 million (0·8–2·1) deaths in unvaccinated children over 20 years. We project thatShigellavaccination could avert 43 million (13−92) stunting cases and 590 000 (297 000–983 000) deaths over 20 years. The overall mean incremental cost-effectiveness ratio (ICER) was US$849 (95% uncertainty interval 423–1575; median $790 [IQR 635–1005]) per disability-adjusted life-year averted. Vaccination was most cost-effective in the WHO African region and in low-income countries. Including the burden ofShigella-related less severe diarrhoea improved mean ICERs by 47−48% for these groups and substantially improved ICERs for other regions.InterpretationOur model suggests thatShigellavaccination would be a cost-effective intervention, with a substantial impact in specific countries and regions. Other regions could potentially benefit upon the inclusion of the burden ofShigella-related stunting and less severe diarrhoea in the analysis.FundingBill & Melinda Gates Foundation and Wellcome Trust.