Musculoskeletal modeling, typically implemented using marker-based systems in laboratory environments, is commonly used for noninvasive estimations of loads. Inertial measurement units (IMUs) have become an alternative for the evaluation of kinematics. However, estimates of spine joint contact forces using IMUs have yet to be thoroughly evaluated. Dynamics tasks and static postures from activities of daily living were captured on 11 healthy subjects using both systems simultaneously. Spine kinematics obtained from IMU- and marker-based systems and L4–L5 joint contact forces were compared. Lateral bending resulted in a weak agreement with significant differences between the 2 systems (P = .02, average root mean-squared error = 4.81), whereas flexion–extension and axial rotation exhibited the highest agreement with no significant differences (P < .05, average root mean-squared error = 5.51 and P < .31, average root mean-squared error = 5.08, respectively). All tasks showed excellent correlations (R2 = .76–.99) in estimated loads between systems. Differences in predicted loads at the L4–L5 were only observed during flexion–extension (1041 N vs 947 N, P = .0004) and walking with weights (814 N vs 727 N, P = .004). Different joint reaction force outcomes were obtained in 2 of the 8 tasks between systems, suggesting that IMUs can be robust tools allowing for convenient and less expensive evaluations and for longitudinal assessments inside and outside the laboratory setting.