Irreversible electroporation (IRE) is an ablation technique based on the application of short, high-voltage pulses between needle electrodes (diameter: ~1.0 × 10−3 m). A Finite Difference-based software simulating IRE treatment generally uses rectangular grids, yielding discretization issues when modeling cylindrical electrodes and potentially affecting the validity of treatment planning simulations. Aim: Develop an Electric-Potential Estimation (EPE) method for accurate prediction of the

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... ic-potential distribution in the vicinity of cylindrical electrodes. Methods: The electric-potential values in the voxels neighboring the cylindrical electrode voxels were corrected based on analytical solutions derived for coaxial/cylindrical electrodes. Simulations at varying grid resolutions were validated using analytical models. Low-resolution heterogeneous simulations at 2.0 × 10−3 m excluding/including EPE were compared with high-resolution results at 0.25 × 10−3 m. Results: EPE significantly reduced maximal errors compared to analytical results for the electric-potential distributions (26.6–71.8%→0.4%) and for the electrical resistance (30%→1–6%) at 3.0 × 10−3 m voxel-size. EPE significantly improved the mean-deviation (43.1–52.8%→13.0–24.3%) and the calculation-time gain (>15,000×) of low-resolution compared to high-resolution heterogeneous simulations. Conclusions: EPE can accurately predict the potential distribution of neighboring cylindrical electrodes, regardless of size, position, and orientation in a rectangular grid. The simulation time of treatment planning can therefore be shortened by using large voxel-sized models without affecting accuracy of the electric-field distribution, enabling real-time clinical IRE treatment planning.