In this paper, we present a new methodology for subject-specific finite element modeling of the tibiofemoral joint based on in vivo computed tomography (CT), magnetic resonance imaging (MRI), and dynamic stereo-radiography (DSX) data. We implemented and compared two techniques to incorporate in vivo skeletal kinematics as boundary conditions: one used MRI-measured tibiofemoral kinematics in a nonweight-bearing supine position and allowed five degrees of freedom (excluding flexion-extension) at the joint in response to an axially applied force; the other used DSX-measured tibiofemoral kinematics in a weight-bearing standing position and permitted only axial translation in response to the same force. Verification and comparison of the model predictions employed data from a meniscus transplantation study subject with a meniscectomized and an intact knee. The model-predicted cartilage-cartilage contact areas were examined against “benchmarks” from a novel in situ contact area analysis (ISCAA) in which the intersection volume between nondeformed femoral and tibial cartilage was characterized to determine the contact. The results showed that the DSX-based model predicted contact areas in close alignment with the benchmarks, and outperformed the MRI-based model: the contact centroid predicted by the former was on average 85% closer to the benchmark location. The DSX-based FE model predictions also indicated that the (lateral) meniscectomy increased the contact area in the lateral compartment and increased the maximum contact pressure and maximum compressive stress in both compartments. We discuss the importance of accurate, task-specific skeletal kinematics in subject-specific FE modeling, along with the effects of simplifying assumptions and limitations.