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3-D interconnect techniques in multilayer very large scale integration design, such as stacked layers and various chip-stacking systems, have paved the way for the improvement of integrated circuit density and operation speed. However, these techniques often accompany with impedance discontinuities that induce signal integrity (SI)/power integrity and electromagnetic interference effects. Consequently, SI analysis serves as one of the key guidelines of chip-package-board design in deep submicrometer technology. However, full-wave numerical analysis of 3-D high-speed and high-density interconnects is also considered to be a great challenge. In this paper, a nonconformal domain decomposition method with second-order transmission condition for SI analysis of high-speed interconnects on a multiscale multilayer printed circuit board is presented. The accuracy and robustness of the proposed method are first witnessed by modeling a six-layer two-trace differential pair. Then we study a 14-layer 16-trace interconnect model to demonstrate the efficiency of the method. Eye diagrams of the two models are also presented in the time-domain SI analysis.