The pulsating heat pipe (PHP) is essentially a two-phase heat transfer device for low heat power applications (heat sinks, electronic cooling, etc.). Although it is a simple, cheap, and flexible structure, it is ruled by very complex physics, and a robust, validated simulation tool is still missing. In the present work the basic numerical model by Holley and Faghri (2005) has been updated with the latest fluid properties database and with the latest nondimensional heat transfer correlations in order to make it suitable for different working fluids. Good agreement between numerical results and experimental data coming from a single-loop PHP operating with ethanol is shown and, using a single “tuning” parameter, that is, the liquid film thickness around a vapor slug, which needs to be further experimentally investigated, the final goal of building a design tool for the PHP construction and implementation is getting closer.