Two-dimensional deep-learning pose estimation algorithms can suffer from biases in joint pose localizations, which are reflected in triangulated coordinates, and then in 3D joint angle estimation. Pose2Sim, our robust markerless kinematics workflow, comes with a physically consistent OpenSim skeletal model, meant to mitigate these errors. Its accuracy was concurrently validated against a reference marker-based method. Lower-limb joint angles were estimated over three tasks (walking, running, and cycling) performed multiple times by one participant. When averaged over all joint angles, the coefficient of multiple correlation (CMC) remained above 0.9 in the sagittal plane, except for the hip in running, which suffered from a systematic 15° offset (CMC = 0.65), and for the ankle in cycling, which was partially occluded (CMC = 0.75). When averaged over all joint angles and all degrees of freedom, mean errors were 3.0°, 4.1°, and 4.0°, in walking, running, and cycling, respectively; and range of motion errors were 2.7°, 2.3°, and 4.3°, respectively. Given the magnitude of error traditionally reported in joint angles computed from a marker-based optoelectronic system, Pose2Sim is deemed accurate enough for the analysis of lower-body kinematics in walking, cycling, and running.