Importance Lateral ankle sprains (LAS) are common in the general population and may lead to chronic ankle instability (CAI). If patients at risk could be identified, they could receive adequate and on-time treatment. Objective The purpose of the current review was to identify all reported intrinsic factors associated with sustaining a LAS or progressing to CAI after an initial sprain. Evidence review PubMed, Embase, MEDline, Cochrane and PEDro were searched for studies published until July 2019. Articles were selected if they included intrinsic factors related to LAS or CAI, subjects of at least 16 years old, and contained a minimum of 10 patients and 10 controls. Studies were excluded if they concerned reviews or case reports, included patients with previous surgical interventions, concomitant injuries or joint pathology other than ankle instability. Quality of included studies was assessed using the Quality in Prognostic Studies tool and quality of evidence was assessed using the GRADEpro tool. In case outcomes were described by at least three studies, data were pooled and assessed by performing a meta-analysis. Based on the pooled data, either a fixed-effects model or random-effects model was selected to correct for the degree of heterogeneity. Findings The search resulted in a total of 4154 studies. After title and abstract screening and subsequent full-text screening, 80 relevant studies were included. Results of the meta-analyses indicated that, compared with healthy controls, patients with LAS had a higher mean body mass index (BMI). In patients with CAI, a higher weight and a longer time to stabilise after performing a task (eg, jumping) were found compared with healthy controls. Other outcomes could not be compared using a meta-analysis due to heterogeneity in outcome measurement and the great number of different outcomes reported. Identification of the risk factors when patients present themselves after a LAS may help to determine which patients are at risk of recurrent sprains or developing CAI. Conclusions and relevance Based on the findings in this review, a higher BMI, and a higher weight and neuromuscular stability deficits may be regarded risk factors for sustaining a LAS or developing CAI, respectively. Level of evidence III.