A design methodology is disclosed for optimizing guard ring design by optimizing the guard ring to power supply path resistance value between physical and/or virtual injection sources in a CMOS circuit and the corresponding power supply. By comparing the calculated guard ring to power supply path resistance value to resistance criteria derived from specifications, elements that need further redesign are identified. Repeated redesign with several redesign options eventually lead to an optimized guard ring structure that provides area-efficient and sufficient latchup protection for the CMOS circuit.