Background Musculoskeletal (MSK) models based on literature data are meant to represent a generic anatomy and are a popular tool employed by biomechanists to estimate the internal loads occurring in the lower limb joints, such as joint reaction forces (JRFs). However, since these models are normally just linearly scaled to an individual’s anthropometry, it is unclear how their estimations would be affected by the personalization of key features of the MSK anatomy, one of which is the femoral version angle. Research Question How are the lower limb JRF magnitudes computed through a generic MSK model affected by changes in the femoral version? Methods We developed a bone-deformation tool in MATLAB (shared at https://simtk.org/projects/bone_deformity) and used it to create a set of seven OpenSim models spanning from 2˚ femoral retroversion to 40˚ anteversion. We used these models to simulate the gait of an elderly individual with an instrumented prosthesis implanted at their knee joint (5th Grand Challenge dataset) and quantified both the changes in JRFs magnitude due to varying the skeletal anatomy and their accuracy against the correspondent in vivo measurements at the knee joint. Results Hip and knee JRF magnitudes were affected by the femoral anteversion with variations from the unmodified generic model up to 11.7 ± 5.5% at the hip and 42.6 ± 31.0% at the knee joint. The ankle joint was unaffected by the femoral geometry. The MSK models providing the most accurate knee JRFs (root mean squared error: 0.370 ± 0.068 body weight, coefficient of determination: 0.757 ± 0.104, peak error range: 0.09-0.42 body weight) were those with femoral anteversion angle closer to that measured on the segmented bone of the individual. Significance Femoral version substantially affects hip and knee JRFs estimated with generic MSK models, suggesting that personalizing key MSK anatomical features might be necessary for accurate estimation of JRFs with these models.