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As technology scales down, more transistors integrate in a single die and the thermal issue becomes a major concern. High operation temperature degrades performance of MOS devices and induce reliability problem. In this paper, the temperature dependence of MOS drain current is analyzed in both linear and saturation regions. It is shown that the drain current is invariable in some specific operation points but may increase or decrease in other operation points with the temperature fluctuation. These temperature-insensitive operation points are derived with analytical formulas and verified with SPICE simulation in 180-nm CMOS technology. In linear region, the temperature-invariant drain current requires a linear relationship between gate-source voltage and drain-source voltage. In saturation region, the drain current mainly relies on gate-source voltage and the temperature-insensitive gate-source voltage is a constant for a given technology. Consequently, the supply voltage can be optimized for temperature-variation-insensitive performance, which is about 42% lower than the nominal supply voltage in a 180-nm CMOS technology.