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We propose an approach to evaluate the effect on the threshold-voltage dispersion of nanoscale metal-oxide-semiconductor field-effect transistors (MOSFETs) of line-edge roughness, surface roughness, and random dopant distribution. The methodology is fully based on parameter sensitivity analysis, performed by means of a limited number of technology computer-aided design simulations or analytical modeling. We apply it to different nanoscale transistor structures, i.e., bulk 45-nm n-channel, 32-nm ultrathin-body silicon-on-insulator, and 22-nm double-gate MOSFETs. In all cases, our approach is capable of reproducing with very good accuracy the results obtained through 3-D atomistic statistical simulations at a small computational cost. We believe that the proposed approach can be a powerful tool to understand the role of the main variability sources and to explore the device design parameter space.