Bonding wire is one of the main interconnection techniques. Thick bonding wire is widely used in power modules and other high power applications. This study examined the case for extending the use of traditional thin wire reliability criteria, namely wire flexure and aspect ratio, to thick wires. Eleven aluminum (Al) and aluminum coated copper (CucorAl) wire samples with diameter 300 μm were tested experimentally. The wire response was measured using a novel non-contact method. High fidelity FEM models of the wire were developed and validated. We found that wire flexure is not correlated to its stress state or fatigue life. On the other hand, aspect ratio is a consistent criterion of thick wire fatigue life. Increasing the wire aspect ratio lowers its critical stress and increases its fatigue life. Moreover, we found that CucorAl wire has superior performance and longer fatigue life than Al wire.