Methods according to the present invention provide computationally efficient techniques for designing gauge patterns for calibrating a model for use in a simulation process. More specifically, the present invention relates to methods of designing gauge patterns that achieve complete coverage of parameter variations with minimum number of gauges and corresponding measurements in the calibration of a lithographic process utilized to image a target design having a plurality of features. According to some aspects, a method according to the invention includes transforming the space of model parametric space (based on CD sensitivity or Delta TCCs), then iteratively identifying the direction that is most orthogonal to existing gauges' CD sensitivities in this new space, and determining most sensitive line width/pitch combination with optimal assist feature placement which leads to most sensitive CD changes along that direction in model parametric space.