We propose an efficient Hermite spline-based SPICE simulation methodology for accurate statistical yield analysis. Unlike conventional methods, the spline-based transistor tables are built on-demand specific to the transient simulation requirements of the statistical experiments. Compared with traditional MOSFET table models, on-demand spline table models use 500X less memory. This makes Hermite spline-based table models practical for use in simulations for process variation modeling. Furthermore, we propose an efficient gate voltage offset approach to model transistor threshold voltage variation. In this scenario, evaluations of the transistor model rely on a single reference table and require one set of spline function evaluations per V T sample point as opposed to two or more sets for V T interpolation. This method is comprehensive and the results are in excellent agreement with traditional BSIM-based simulations. Around 4X improvement in speed, which includes the table generation cost, could be further improved by employing other fast-SPICE techniques or parallelism. To the best of our knowledge, this is the first time such a methodology has been coupled with importance sampling techniques to study the yield of memory designs. © 2011 IEEE.