Knowing the forces in the human body is of great clinical interest and musculoskeletal (MS) models are the most commonly used tool to estimate them in vivo. Unfortunately, the process of computing muscle, joint contact, and ligament forces simultaneously is computationally highly demanding. The goal of this study was to develop a fast surrogate model of the tibiofemoral (TF) contact in a total knee replacement (TKR) model and apply it to force-dependent kinematic (FDK) simulations of activities of daily living (ADLs). Multiple domains were populated with sample points from the reference TKR contact model, based on reference simulations and design-of-experiments. Artificial neural networks (ANN) learned the relationship between TF pose and loads from the medial and lateral sides of the TKR implant. Normal and right-turn gait, rising-from-a-chair, and a squat were simulated using both surrogate and reference contact models. Compared to the reference contact model, the surrogate contact model predicted TF forces with a root-mean-square error (RMSE) lower than 10 N and TF moments lower than 0.3 N·m over all simulated activities. Secondary knee kinematics were predicted with RMSE lower than 0.2 mm and 0.2 deg. Simulations that used the surrogate contact model ran on average three times faster than those using the reference model, allowing the simulation of a full gait cycle in 4.5 min. This modeling approach proved fast and accurate enough to perform extensive parametric analyses, such as simulating subject-specific variations and surgical-related factors in TKR.