In osteoarthritis (OA) research it is increasingly recognized that stratification according to disease phenotypes is essential for optimizing treatment regimens. Gender-specific differences in clinical OA manifestations have been identified, and this analysis aimed to assess whether these differences extend to imaging phenotypes.From the Osteoarthritis Initiative database 2523 participants (1409 women and 1114 men) with completed 3T MRI and whole-organ magnetic resonance imaging scores (WORMS) of the right knee at baseline were included. Imaging phenotypes were assigned based on modified Rapid OsteoArthritis MRI Eligibility Score: the inflammatory, meniscus-cartilage, and bone phenotype. Logistic regression was performed to investigate the effect of gender on phenotype, independent of BMI, race, Kellgren & Lawrence (KL) grade and level of physical activity. Female gender was independently associated with lower odds for the meniscus-cartilage (OR 0.61, 95%CI 0.47-0.80, p <
0.001) but not for the inflammatory (OR 1.04, 95%CI 0.89-1.24, p = 0.697) or the subchondral bone phenotype (OR 1.13, 95%CI 0.95-1.36, p = 0.166). This difference highlights an opportunity for future refinements to better accommodate gender/sex differences in disease trajectories while investigating different treatment regimes in knee OA.