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Current methods for center-of-mass (CoM) estimation are restricted to gait laboratories. The aim of this study was to estimate CoM displacement under ambulatory conditions with inertial sensors. A sacral inertial sensor (SIS method) was used to estimate the CoM displacement by double integration of the acceleration. Overestimation of the displacement caused by pelvic rotations was compensated (CSIS method). The CoM displacement estimations using the (C)SIS method were compared to the conventional methods of the segmental analysis (SA) method and the sacral marker (SM) method by the intraclass correlations and the root-mean-square (RMS) differences between the CoM curves. Accurate ambulatory measurement of the CoM displacement using inertial sensors was possible. Estimations of the sacrum position using the SIS method and the SM method were similar with mean (SD) RMS differences of 3.23 (0.87), 2.96 (0.42), and 3.22 (0.78) mm for, respectively, the x-, y- and z-directions. The CoM estimation of the SIS method has RMS differences of 5.67 (1.20), 7.16 (3.28), and 3.49 (1.29) mm compared the SA method. The CSIS method shows a clear improvement in these estimations of the CoM with RMS differences of 5.52 (1.29), 4.44 (1.89), and 3.17 (1.41) mm and is generally applicable for healthy subjects.