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Copper wire bonding is an alternative interconnection technology promising cost savings compared to gold wire bonding and better electrical performance compared to aluminum wire. In this paper, ultrasonic wedge bonding with 25μm copper wire on Au/Ni/Cu metallization of a PCB substrate was performed at ambient temperature. A central composite design of experiment (DOE) approach was applied to optimize the copper wire wedge bonding process parameters. Pull testing of the wedge bond was performed to study the bond strength and to find the optimum bonding parameters. Scanning electron microscopy (SEM) was used to observe the wedge bond cross sections. The results show that it is possible to produce strong copper wire wedge bonds. The DOE results gave the optimized parameters for both the first bond and the second bond. Cross section analysis shows a continuous interconnection between the copper wire and Au/Ni/Cu metallization. The thickness of the Au layer decreased with the bonding power increasing.