Irreversible electroporation (IRE) is a novel method to ablate abnormal cells by applying a high voltage between the electrodes punctured in abnormal tissues. The cell membrane exposed to the potential difference above a certain threshold is permanently disrupted, which consequently induces cell necrosis. One of the advantages of the IRE is that the extracellular matrix (ECM) can be kept intact, which is favorable for healing. Thus, it is important to determine an optimal condition of electric pulses and electrode configuration prior to a clinical application so that a proper volume of the targeted tissue is ablated without thermal damage resulted from the Joule heating. The aims of this study were, therefore, to estimate the possible temperature rise during the IRE by a nondimensional 3-D analysis, and to reveal the risk of ECM denaturation caused by the IRE parameters such as electrode dimension, the distance between two electrodes, and the applied voltage. The heat conduction equation and the Laplace equation in nondimensional forms were solved numerically using the finite element method for the IRE with a pair of rod-shaped electrodes placed in a simulated tissue. Numerical analysis clarified that concentration of electric current induced local heat generation, which resulted in the formation of hot spots near the base and the tip of electrodes. The highest temperature rise occurred at the base of electrodes adjacent to the insulated surface. The result was significantly different from a two-dimensional (2-D) analysis due to end effects, suggesting that the 3-D analysis is required to determine the optimal condition. The region of ablated tissue and its volume were also shown as a function of IRE parameters. This provides useful information for a preoperative simulation of the IRE. Finally, the accumulation of the thermal damage was estimated for three kinds of tissue, i.e., epidermis, aorta, and skin collagen. Although the IRE usually uses a short electric pulse duration from several ten to hundred microseconds, our study demonstrated that even the short pulses in the order of hundred microseconds have a risk for the thermal denaturation depending on tissues and the pulse magnitude. (C) 2014 Elsevier Ltd. All rights reserved.