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The simultaneous application of voltage scaling, repeater insertion, and wire sizing is proposed in this paper to achieve high performance, low power, and low area on wave-pipelined interconnect circuits. Based on this methodology, design optimizations for three different types of applications are performed and different design metrics are used to obtain the optimal values of supply voltage, number of repeaters, and interconnect dimensions for these applications. The optimal supply voltage for low-power applications is shown to be twice the threshold voltage. In addition, an optimal throughput-per-energy-area (TPEA) design is compared with low-voltage differential signaling (LVDS). The optimal TPEA design is shown to reduce dynamic power by 10% and wire area by 70% compared to LVDS, without any loss of throughput performance.