The choice of marker set is a source of variability in motion analysis. Studies exist which assess the performance of marker sets when direct kinematics is used, but these results cannot be extrapolated to the inverse kinematic framework. Therefore, the purpose of this study was to examine the sensitivity of kinematic outcomes to inter-marker set variability in an inverse kinematic framework. The compared marker sets were plug-in-gait, University of Ottawa motion analysis model and a three-marker-cluster marker set. Walking trials of 12 participants were processed in opensim. The coefficient of multiple correlations was very good for sagittal (>0.99) and transverse (>0.92) plane angles, but worsened for the transverse plane (0.72). Absolute reliability indices are also provided for comparison among studies: minimum detectable change values ranged from 3 deg for the hip sagittal range of motion to 16.6 deg of the hip transverse range of motion. Ranges of motion of hip and knee abduction/adduction angles and hip and ankle rotations were significantly different among the three marker configurations (P < 0.001), with plug-in-gait producing larger ranges of motion. Although the same model was used for all the marker sets, the resulting minimum detectable changes were high and clinically relevant, which warns for caution when comparing studies that use different marker configurations, especially if they differ in the joint-defining markers.