Background: Many factors are thought to contribute to chronic ankle instability (CAI). Multiple systematic reviews have synthesised the available evidence to identify the primary contributing factors. However, readers are now faced with several systematic reviews that present conflicting findings. Objective: The aim of this systematic review and meta-analysis was to establish the statistical significance and effect size of primary factors contributing to CAI and to identify likely reasons for inconsistencies in the literature. Methods: Relevant health databases were searched: CINAHL, MEDLINE, PubMed, Scopus and SPORTDiscus. Systematic reviews were included if they answered a focused research question, clearly defined the search strategy criteria and study selection/inclusion and completed a comprehensive search of the literature. Included reviews needed to be published in a peer-reviewed journal and needed to review observational studies of factors and/or characteristics of persons with CAI, with or without meta-analysis. There was no language restriction. Studies using a non-systematic review methodology (e.g. primary studies and narrative reviews) were excluded. Methodological quality of systematic reviews was assessed using the modified R-AMSTAR tool. Meta-analysis on included primary studies was performed. Results: Only 17% of primary studies measured a clearly defined CAI population. There is strong evidence to support the contribution of dynamic balance, peroneal reaction time and eversion strength deficits and moderate evidence for proprioception and static balance deficits to non-specific ankle instability. Conclusions: Evidence from previous systematic reviews does not accurately reflect the CAI population. For treatment of non-specific ankle instability, clinicians should focus on dynamic balance, reaction time and strength deficits; however, these findings may not be translated to the CAI population. Research should be updated with an adequately controlled CAI population. Systematic review registration: PROSPERO 2016, CRD42016032592.