BACKGROUND: Ankle sprains are one of the most common musculoskeletal injuries. In order to evaluate the effectiveness of therapeutic interventions and to guide management decisions, it is important to have clear insight of the course of recovery after an acute lateral ankle injury and to evaluate potential factors for nonrecovery and re-sprains. METHODS: A database search was conducted in MEDLINE, CINAHL, PEDro, EMBASE, and the Cochrane Controlled trial register. Included were observational studies and controlled trials with adult subjects who suffered from an acute lateral ankle sprain that was conventionally treated. One of the following outcomes had to be described: pain, re-sprains, instability, or recovery. Two reviewers independently assessed the methodological quality of each included study. One reviewer extracted relevant data. RESULTS: In total, 31 studies were included, from which 24 studies were of high quality. There was a rapid decrease in pain reporting within the first 2 weeks. Five percent to 33% of patients still experienced pain after 1 year, while 36% to 85% reported full recovery within a period of 3 years. The risk of re-sprains ranged from 3% to 34% of the patients, and re-sprain was registered in periods ranging from 2 weeks to 96 months postinjury. There was a wide variation in subjective instability, ranging from 0% to 33% in the high-quality studies and from 7% to 53% in the low-quality studies. One study described prognostic factors and indicated that training more than 3 times a week is a prognostic factor for residual symptoms. CONCLUSIONS: After 1 year of follow-up, a high percentage of patients still experienced pain and subjective instability, while within a period of 3 years, as much as 34% of the patients reported at least 1 re-sprain. From 36% up to 85% of the patients reported full recovery within a period of 3 years.