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In this paper, we estimate the effect of random work function (WK) on the threshold voltage fluctuation (σVth) of 16-nm-gate metal-oxide-semiconductor field-effect transistors (MOSFETs) with metal-gate materials. To examine the random WK induced σVth, nanosized metal grains with different gate materials are considered in a large-scale statistical simulation. An analytical expression of the WK induced σVth is proposed based on the Monte Carlo simulation results which can outlook different extents of fluctuation resulting from various metal gates and benefit the device fabrication. Devices with a two-layer metal-gate are further studied for fluctuation suppression; the finding of this paper indicates the first layer of the gate structure plays the most significant role in the suppression of the WK induced σVth, compared with the second layer. This paper provides an insight into random work-function-induced threshold voltage fluctuation, which can, in turn, be used to assess metal gate characteristics of MOSFETs.