Background Consumption of unsafe foods increases morbidity and mortality and is currently an issue, particularly in low- and middle-income countries. Policy actions to ensure food safety are dominated by mitigation of biological and chemical hazards through supply-side risk management, lessening the degree to which consumer perspectives of food safety are considered. Objective This study aimed to provide an in-depth understanding, from vendor and consumer perspectives, of how food safety concerns of consumers translate into their subsequent food choice behaviors in six diverse low- and middle-income countries. Methods Six Drivers of Food Choice projects (2016-2022) provided transcripts from 17 focus group discussions and 343 interviews in Ghana, Guinea, India, Kenya, Tanzania, and Vietnam. Qualitative thematic analysis was used to identify emerging themes important to food safety. Results The analysis suggests that consumers constructed meaning about food safety through personal lived experience and social influences. Community and family members contributed knowledge about food safety. Concerns about food safety were influenced by reputations of, and relationships with, food vendors. Consumers’ mistrust of food vendors was amplified by purposeful adulteration or unsafe selling practices and new methods used to produce food. Consumers were reassured of food safety by positive relationships with vendors; meals cooked at home; implementation of policies and following of regulations; vendor adherence to environmental sanitation and food hygiene practices; cleanliness of vendors’ appearance; and vendors’ or producers’ agency to use risk mitigation strategies in production, processing, and distribution of food. Conclusions Consumers integrated their meanings, knowledge, and concerns about food safety to achieve assurance about the safety of their foods when making food choice decisions. The success of food-safety policies hinges on consideration of consumers’ food safety concerns in their design and implementation, alongside actions to reduce risk in food supply.