The objective of this study was to evaluate biomechanical response differences in human ribs subjected to simplified anterior-posterior (AP) dynamic loading versus AP loading combined with lateral (AP-L). Twelve bilateral pairs of 6th human ribs from an age-distributed sample (54 ± 17 years) were included in this study. One rib within each pair was selected to undergo 2D simplified AP loading to failure at 2 m/s. The other rib within the pair was tested in the same AP scenario, but with the added element of a rigid plate to constrain lateral displacement (AP-L). This set-up was intended to simply represent the combined AP and lateral loading the thorax would experience with a shoulder-belt pretensioner and a side airbag in a side impact. Results showed a significant response difference in time to fracture, displacement, peak force, and structural stiffness between AP only and AP-L tests. This work highlights the complexity of combined loading on human ribs that has not previously been investigated, and provides important evidence to explore variability in whole thoracic response and injury severities in various scenarios with different combinations of restraints in physical and simulated experiments.