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In this paper, we propose an efficient and accurate full-chip thermomechanical stress and reliability analysis tool and design optimization methodology to alleviate mechanical reliability issues in 3-D integrated circuits (ICs). First, we analyze detailed thermomechanical stress induced by through-silicon vias in conjunction with various associated structures such as landing pad and dielectric liner. Then, we explore and validate the linear superposition principle of stress tensors and demonstrate the accuracy of this method against detailed finite element analysis simulations. Next, we apply this linear superposition method to full-chip stress simulation and a reliability metric named the von Mises yield criterion. Finally, we propose a design optimization methodology to mitigate the mechanical reliability problems in 3-D ICs. Our numerical experimental results demonstrate the effectiveness of the proposed methodology.