Objective: Ankle osteoarthritis (OA) has a prevalence of 3.4% in the general population of which 70% to 78% is posttraumatic, affecting younger patients with a longer projected life span compared with hip and knee OA. The current literature reports the physical and mental quality of life (QoL) of patients with ankle OA, to be similar to end-stage hip OA, end-stage kidney disease and digestive heart failure. However, the QoL of ankle OA patients has not yet been determined compared with a matched control group representing the general population. Our aim is to determine the physical and mental QoL compared with a matched control group. Design: The Physical and Mental Component Summaries of the Short Form–36 of 100 patients with ankle OA were compared with 91 age- and gender-matched controls. This case-control study is a substudy of the PRIMA trial, in which the efficacy of platelet-rich plasma injections for ankle OA is determined. Results: A clinically relevant difference was found for both the Physical (P=0.003; 95% CI −6.7 to −1.3) and Mental Component Summary scores (P < 0.001; 95% CI −10 to −6). Patients with ankle OA had a median of 45 points (matched controls 52 points) and 43 points (matched controls 53 points) for the Physical and Mental Component summary scores, respectively. Conclusions: Patients with ankle OA had a clinically relevant poorer mental and physical QoL compared with matched controls from the general population. Furthermore, the physical QoL of patients with ankle OA from younger age categories was affected more than those in older age categories.