Purpose <p>Although severe pain caused by progressive ankle osteoarthritis (OA) impairs patients’ quality of life, factors associated with severe pain in ankle OA are unknown. This study aimed to analyze the characteristics of pain and the association between pain, radiographic alignment, and computed tomography (CT) and magnetic resonance imaging (MRI) findings in patients with varus ankle OA.</p> Methods <p>Seventy-five ankles from 73 patients with varus ankle OA who underwent surgery were retrospectively reviewed. Pain was evaluated using the self-administered foot evaluation questionnaire (SAFE-Q). Ankle alignment was assessed by radiography. Subchondral bone sclerosis was assessed by CT-derived Hounsfield unit (HU) ratio, and synovitis and bone marrow edema (BME) were assessed by MRI. The relationship between pain and imaging findings was analyzed.</p> Results <p>Pain and pain-related scores in the SAFE-Q significantly correlated with the Takakura-Tanaka classification stage (<i>r</i> = − 0.529), osteophyte score (<i>r</i> = − 0.460), HU ratios (<i>r</i> = − 0.729), synovial thickness score (<i>r</i> = − 0.387), and BME area (<i>r</i> = − 0.475). Multivariate analysis revealed that high HU ratio, progressed OA stage, and thick synovium were significantly associated with severe pain. Notably, HU ratios showed moderate to strong correlations with pain, regardless of radiographic severity, even in the regions where joint space was radiographically preserved.</p> Conclusions <p>Subchondral bone sclerosis, OA severity, and synovitis are significantly correlated with pain in patients with varus ankle OA. The novel finding is that HU ratios of subchondral bone correlate with pain irrespective of radiographic stage, suggesting that severe pain reflects hidden mechanical stress and cartilage degeneration associated with subchondral sclerosis. Varus ankle OA with severe pain should be managed early and appropriately, regardless of radiographic severity.</p> Level of evidence <p>III.</p>