This study aimed to introduce and validate a new method to estimate and correct the orientation drift measured from foot-worn inertial sensors. A modified strap-down integration (MSDI) was proposed to decrease the orientation drift, which, in turn, was further compensated by estimation of the joint center acceleration (JCA) of a two-segment model of the foot. This method was designed to fit the different foot strike patterns observed in running and was validated against an optical motion-tracking system during level treadmill running at 8, 12, and 16 km/h. The sagittal and frontal plane angles obtained from the inertial sensors and the motion tracking system were compared at different moments of the ground contact phase. The results obtained from 26 runners showed that the foot orientation at mean stance was estimated with an accuracy (inter-trial median ± IQR) of 0.4 ± 3.8° and a precision (inter-trial precision median ± IQR) of 3.0 ± 1.8°. The orientation of the foot shortly before initial contact (IC) was estimated with an accuracy of 2.0 ± 5.9° and a precision of 1.6 ± 1.1°; which is more accurate than commonly used zero-velocity update methods derived from gait analysis and not explicitly designed for running. Finally, the study presented the effect initial and terminal contact (TC) detection errors have on the orientation parameters reported.