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In this study, a combination of experiments and analyses are performed to characterize the structural response of two variable stiffness composite panels to a series of thermal and mechanical loads. This characterization covers all phases of the structure’s lifetime from design through global failure. These panels are advanced composite structures in which the fiber orientation angle varies continuously as tows are laid down along predefined curvilinear paths within each ply. The panels are manufactured from AS4/977-3 graphite-epoxy prepreg using an advanced tow placement system. Both variable stiffness panels have the same nominal layup, but one panel (the panel with overlaps) has overlapping tow bands of varying thickness and the other panel (the panel without overlaps) has a theoretically uniform-thickness laminate. A conventional uniform-thickness panel with a straight-fiber [±45]5s layup (the baseline panel) is also evaluated to provide a reference for comparison of the variable stiffness panel performance.