Modern decananometer-sized MOS transistors tend to exhibit high rates of failure, underscoring the need for accurately estimating the unreliabilities of circuits built from such transistors. This paper presents a methodology for unreliability calculation that extends from individual transistors to complete logic circuits. As a logic cell’s or logic circuit’s unreliability is highly dependent on its transistors’ drain–source and gate–source voltages, SPICE simulations are used to determine the voltages for the individual transistors. The voltage measurements are then utilized by the mathematical equations to predict the unreliabilities with high accuracy. A scalable framework based on the proposed methodology has been successfully implemented. The framework has been validated using ISCAS85 benchmark circuits.