Background: Chronic ankle instability (CAI) is a common result of an ankle sprain. Even though early surgical treatment yields the best results, overall only professional athletes are eligible for acute surgical stabilization. Treating all patients with early surgical stabilization leads to a high amount of unnecessary invasive interventions, as not all patients progress to CAI. If patients at risk of developing CAI can be identified, treatment policies may be applied more effectively and efficiently. The purpose of this study is to develop a risk assessment model to identify patients at risk for CAI that should receive early surgical treatment. Methods: In this observational prospective cohort, all patients aged sixteen years and older, reporting at the emergency department of one of the participating hospitals after sustaining a lateral ankle sprain, and filled out 1 out of 3 follow-up questionnaires and the 1 year follow-up are included. A lateral and anteroposterior radiograph is made. Patients are excluded if a fracture or other pathology is present. The included patients receive four questionnaires, including questions focusing on the sprain, treatment and complaints, the Foot and Ankle Outcome Score and the Cumberland Ankle Instability Tool. A total of eleven radiographic variables are assessed for inter- and intra-observer reliability. Additionally, four factors extracted from the questionnaires, will be evaluated for correlation with CAI. Significantly correlating factors (e.a. risk factors) will be implemented in a risk assessment model. For the final model, based on sixteen variables with a minimum of 20 events per variable and a prevalence of 30-40% after an initial sprain, a sample size of 2370 patients is needed to perform both internal and external model validation. Discussion: This study will develop the first large scale model for the risk at CAI after an ankle sprain combining radiographic and patient characteristics. With this risk assessment model, patients at risk for CAI may be identified and properly informed on the treatment options. Patients identified as being at risk, may receive more adequate follow-up and become eligible for early surgical stabilization. This prevents patients from experiencing unnecessary long-lasting complaints, increasing the success rate of conservative and surgical treatment. Trial registration: Retrospectively registered: NCT02955485 [Registration date: 3-11-2016]. NTR6139 [Registration date: 3-1-2017].