One hundred patients with ankle osteoarthritis were randomly assigned to receive either intra-articular platelet-rich plasma injections (PRP; n=48) or intra-articular placebo injections (n=52). The primary outcome was the patient-reported American Orthopaedic Foot & Ankle Society (AOFAS) score over 52 weeks. Secondary outcomes included various patient-reported measures assessing pain, function, quality of life, and indirect costs over the same period. The adjusted between-group difference for the patient-reported AOFAS score at 52 weeks favored the placebo group by 2 points (95% CI, 25 to 2; P = .31). With regards to secondary outcomes, there were no statistically significant between-group differences observed as was measured at 52 weeks post procedure. Overall, this indicates that PRP injections did not significantly improve ankle symptoms and function compared to placebo.