Osteoarthritis (OA) is a common, degenerative joint disease that causes painful movement, and persons with OA report limitations in performing daily activities and feeling “wobbly” or “unsteady” due to their affected limb. Physical therapy intervention may be beneficial for those with moderate OA, and physical therapists commonly administer functional assessment tests which mimic or incorporate activities of daily living (ADL), including the sit-tostand transfer task. To administer effective therapy, clinicians aim to target the mechanisms underlying pathologies as illustrated by both functional and self-report assessments. In order to develop effective therapy strategies based off an individual’s functional performance, we need to understand the forces in and contributions of individual muscles during movement, which cannot be determined by experiments alone. We created three-dimensional, muscle-driven simulations of subjects with severe OA completing the STS task and found that the gluteus maximus and vastus lateralis produced the largest forces across the STS trial, while soleus was the largest contributor to both horizontal and vertical acceleration of the COM, and vastus lateralis was the largest resistor to the horizontal propulsion of the COM. Our results were compared to a similar study in a young, healthy population, who found similar conclusions for peak muscle forces and contributions. We also found that the two populations exhibited different kinematics, timing of peak joint torques, and muscle activation patterns for the vasti muscles, plantarflexors, gluteus maximus, and tibialis anterior for various duration of the trial. Subjects with severe OA displayed increased hip flexion across the STS trial, increased knee flexion at the end of the STS trial, and increased dorsiflexion at the beginning of the STS trial, compared to young, healthy subjects. Additionally, OA subjects generated greater hip and ankle joint torques, and less knee joint torque compared to young, healthy subjects. Our simulations estimated that those with OA activated the vasti muscles early in the STS trial and gluteus maximus late in the STS trial, which differed from the activation patterns of young, healthy subjects. This study also suggests potential associations between peak muscle activations and KOOS activities of daily living, quality of life, and pain sub scores, STS trial duration, and timedup-and-go test duration, which lay the foundation for possible correlations between simulated parameters and clinical assessment scores. This work, in combination with simulation of other populations and motion, may provide insight as to which muscles are the largest contributors to movement and which muscles may compensate for weakness due to pathology. With this information, more effective physical therapy programs may be developed to decrease pain and increase function of those with moderate OA.