Wire bond connections are susceptible to fatigue failure as a result of various thermo-mechanical damage mechanisms during the component operation life. Because of uncertainties arising from the random nature of temperature fluctuations, the assembly of wirebonds, and fatigue properties of bonding materials, a probabilistic analysis and reliability estimation are appropriate. This paper presents such an approach for predicting thermal fatigue life and reliability of wire bonds in electronic packages. To determine the behavior of wire bonds under thermal cycles, the stress amplitude due to the temperature fluctuation in each fatigue failure mechanism is derived based on stress analysis models, the uncertainties involved in stress determination and life prediction are analyzed, and a life prediction equation is proposed. Examples illustrating the application of the approach are discussed.