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Introduction Economic sanctions restrict customary commercial and financial ties between states to induce change in political constitution or conduct of the targeted country. Although the stated goals of sanctions often include humanitarian objectives, prospective procedures for health risk assessment are not regularly incorporated in their implementation. Moreover, past experience suggests that the burden of economic isolation may fall on the civilian population. We present key findings from a WHO-sponsored evidence review on the impact of economic sanctions on health and health systems in low-income and middle-income countries, aiming at comprehensive coverage and explicit consideration of issues of causality and mechanisms.Methods Broad searches of PubMed and Google Scholar (1970–2021) were designed to retrieve published and grey English-language literature expected to cut across disciplines, terminology and research methods. Studies providing an impact estimate were rated by a structured assessment based on ROBINS-I risk of bias domains, synthesised via vote counting and contextualised into the broader literature through a thematic synthesis.Results Included studies (185) were mostly peer-reviewed, mostly single-country, largely coming from medicine and public health, and chiefly concerned with three important target countries—Iraq, Haiti and Iran. Among studies providing impact estimates (31), most raised multiple risk-of-bias concerns. Excluding those with data integrity issues, a significant proportion (21/27) reported consistently adverse effects of sanctions across examined outcomes, with no apparent association to assessed quality, focus on early episodes or publication period. The thematic synthesis highlights the complexity of sanctions, their multidimensionality and the possible mechanisms of impact.Conclusion Future research should draw on qualitative knowledge to collect domain-relevant data, combining it with better estimation techniques and study design. However, only the adoption of a risk assessment framework based on prospective data collection and monitoring can certify claims that civilians are adequately protected.