Objectives: To conduct the first systematic review from an epidemiological perspective regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, osteoarthritis (OA) and both first-party and second-party injury in human participants without prior musculoskeletal conditions.Setting: A systematic review of international peer-reviewed scientific literature across seven major languages.Data sources: Searches were conducted on seven major bibliographic databases in July 2015 to initially identify all scholarly articles on high-heeled shoes. Supplementary manual searches were conducted. Titles, abstracts and full-text articles were sequentially screened to identify all articles assessing epidemiological evidence regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, OA and both first-party and second-party injury in human participants without prior musculoskeletal conditions. Standardised data extraction and quality assessment (Threats to Validity tool) were conducted.Primary and secondary outcome measures: Musculoskeletal pain or OA as assessed by clinical diagnosis or clinical assessment tool. First-party or second-party injury.Results: 644 unique records were identified, 56 full-text articles were screened and 18 studies included in the review. Four studies assessed the relationship with hallux valgus and three found a significant association. Two studies assessed the association with OA and neither found a significant association. Five studies assessed the association with musculoskeletal pain and three found a significant association. Eight studies assessed first-party injury and seven found evidence of a significant injury toll associated with high-heeled shoes. One study provided data on second-party injury and the injury toll was low.Conclusions: High-heeled shoes were shown to be associated with hallux valgus, musculoskeletal pain and first-party injury. No conclusive evidence regarding OA and second-party injury was found. Societal and clinical relevance of these findings is discussed. Concern is expressed about the expectation to wear high-heeled shoes in some work and social situations and access by children.