Objectives(1) Assess the distribution of skin-to-deltoid-muscle distance (SDMD) at the deltoid intramuscular (IM) injection site; (2) its relationship with demographic and anthropometric variables and (3) Consider the findings in relation to clinical guidance on IM injection, such as COVID-19 vaccines.DesignSystematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesMEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL and SCOPUS between June and July 2021 with no publication date limit.Eligibility criteriaStudies reporting measurements of the SDMD in living adults aged 16 years and older, at the deltoid IM injection site, published in English were considered.Data extraction and synthesisTwo independent reviewers performed each stage of screening, data extraction and quality assessments using the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross sectional studies.Results16 105 papers were identified, of which 11 studies were suitable for review, representing 1414 participants. Heterogeneity in the definition of the deltoid IM injection site, locations measured and methods of measurement precluded meta-analysis. Evidence from ultrasound SDMD measurements demonstrated some patients in all but ‘underweight’ body mass index (BMI) categories, may require needles longer than 25 mm for successful IM injection. Calliper measurements overestimated SDMD compared with ultrasound. Female sex, higher BMI categories and greater weight in women were associated with greater SDMD.ConclusionsThe reviewed evidence was insufficient to inform definitive needle length ‘cut points’ for IM injection based on demographic or anthropomorphic variables. Contemporary clinical guidance currently based on this evidence, including the site of injection and choice of needle length, may result in subcutaneous administration in a small proportion of recipients, particularly if obese or of female sex.PROSPERO registration numberCRD42021264625.