Purpose <p>Medial meniscus extrusion compromises the ability of meniscus to distribute a load across the knee joint and is recognized as a risk factor for knee osteoarthritis. Despite a positive correlation between medial meniscus extrusion and medial tibial osteophyte width, the sequence of these pathological changes remains unclear. In this multicenter cross-sectional study, we aimed to clarify the relationship between osteophyte formation and medial meniscus extrusion by comparing extrusion distances in knees with and without medial tibial osteophytes.</p> Methods <p>We enrolled 207 Japanese patients with early-stage knee osteoarthritis, defined as Kellgren–Lawrence grade ≤ 2. Participants underwent radiography, magnetic resonance imaging, and ultrasonography (US). Knees were categorized into three groups based on the presence of osteophytes: N (no osteophytes), U (osteophytes detected only with US), and O (osteophytes detected with both radiography and US). The medial meniscus extrusion distance was assessed using US.</p> Results <p>Among the 211 knees evaluated, 89 were classified into the N group, 93 into the U group, and 29 into the O group. The medial meniscus extrusion distance was significantly greater in the O group (3.3 ± 1.3&#xa0;mm) than in both the N (2.3 ± 1.1&#xa0;mm, p &lt; 0.001) and U (2.6 ± 0.9&#xa0;mm, p = 0.004) groups. No significant difference was detected between the N and U groups (p = 0.27).</p> Conclusion <p>Medial meniscus extrusion was significantly associated with osteophyte formation in early-stage knee osteoarthritis.</p>