The patellofemoral (PF) joint plays an essential role in knee function, but little is known about the in vivo loading conditions at the joint. We hypothesized that the forces at the PF joint exceed the tibiofemoral (TF) forces during activities with high knee flexion. Motion analysis was performed in two patients with telemetric knee implants during walking, stair climbing, sit-to-stand, and squat. TF and PF forces were calculated using a musculoskeletal model, which was validated against the simultaneously measured in vivo TF forces, with mean errors of 10% and 21% for the two subjects. The in vivo peak TF forces of 2.9-3.4 bodyweight (BW) varied little across activities, while the peak PF forces showed significant variability, ranging from less than 1 BW during walking to more than 3 BW during high flexion activities, exceeding the TF forces. Together with previous in vivo measurements at the hip and knee, the PF forces determined here provide evidence that peak forces across these joints reach values of around 3 BW during high flexion activities, also suggesting that the in vivo loading conditions at the knee can only be fully understood if the forces at the TF and the PF joints are considered together. Ă