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The nutrition literature and authoritative reports increasingly recognise the concept of ultra-processed foods (UPF), as a descriptor of unhealthy diets. UPFs are now prevalent in diets worldwide. This review aims to identify and appraise the studies on healthy participants that investigated associations between levels of UPF consumption and health outcomes. This involved a systematic search for extant literature; integration and interpretation of findings from diverse study types, populations, health outcomes and dietary assessments; and quality appraisal. Of 43 studies reviewed, 37 found dietary UPF exposure associated with at least one adverse health outcome. Among adults, these included overweight, obesity and cardio-metabolic risks; cancer, type-2 diabetes and cardiovascular diseases; irritable bowel syndrome, depression and frailty conditions; and all-cause mortality. Among children and adolescents, these included cardio-metabolic risks and asthma. No study reported an association between UPF and beneficial health outcomes. Most findings were derived from observational studies and evidence of plausible biological mechanisms to increase confidence in the veracity of these observed associations is steadily evolving. There is now a considerable body of evidence supporting the use of UPFs as a scientific concept to assess the 'healthiness' of foods within the context of dietary patterns and to help inform the development of dietary guidelines and nutrition policy actions.