Introduction Platelet-rich plasma (PRP) is a potentially efficacious treatment for ankle osteoarthritis (OA), but its use has not been examined in high-quality studies. Systematic reviews show that PRP injections significantly decrease pain and improve function in patients with knee OA. Ankle OA is more common than hip or knee OA in the young active population; with a prevalence of 3.4%. PRP injections in ankle OA are shown to be safe and improve quality of life over time, but no randomised controlled trial has been conducted. Our randomised controlled trial will evaluate the efficacy of PRP injections for symptom reduction and functional improvement, compared with placebo, in the treatment of ankle (talocrural) OA. Methods and analysis We will conduct the Platelet-Rich plasma Injection Management for Ankle OA study: a multicentre, randomised, placebo-controlled trial. One hundred patients suffering from ankle OA will be randomised into two treatment groups: PRP injection or placebo (saline) injection. Both groups will receive two injections of PRP or placebo at an interval of 6 weeks. Primary outcome is the American Orthopaedic Foot and Ankle Society score at 26 weeks. Secondary outcomes determined at several follow-up moments up to 5 years, include Ankle Osteoarthritis Score, Foot and Ankle Outcome Score, pain subscale of (0–40), Visual Analogue Scale score (0–100), Ankle Activity Score (0–10), subjective patient satisfaction Short Form Health Survey-36, Global Attainment Scaling and the EuroQol-5 dimensions-3 levels utility score. A cost-effectiveness analysis will be performed at 1 year. Ethics and dissemination The study is approved by the Medical Ethics Review Committee Amsterdam Medical Center, the Netherlands (ABR 2018–042, approved 23 July 2018) and registered in the Netherlands trial register (NTR7261). Results and new knowledge will be disseminated through the Dutch Arthritis Association (ReumaNederland), Dutch patient federation, conferences and published in a scientific peer-reviewed journal. Trial ...