A multi-parametric transient numerical simulation of the start-up of a large diameter Pulsating Heat Pipe (PHP) specially designed for future experiments on the International Space Station (ISS) are compared to the results obtained during a parabolic flight campaign supported by the European Space Agency. Since the channel diameter is larger than the capillary limit in normal gravity, such a device behaves as a loop thermosyphon on ground and as a PHP in weightless conditions; therefore, the microgravity environment is mandatory for pulsating mode. Because of a short duration of microgravity during a parabolic flight, the data concerns only the transient start-up behavior of the device. One of the most comprehensive models in the literature, namely the in-house 1-D transient code CASCO (French acronym for Code Avancé de Simulation du Caloduc Oscillant: Advanced PHP Simulation Code in English), has been configured in terms of geometry, topology, material properties and thermal boundary conditions to model the experimental device. The comparison between numerical and experimental results is performed simultaneously on the temporal evolution of multiple parameters: tube wall temperature, pressure and, wherever possible, velocity of liquid plugs, their length and temperature distribution within them. The simulation results agree with the experiment for different input powers. Temperatures are predicted with a maximum deviation of 7%. Pressure variation trend is qualitatively captured as well as the liquid plug velocity, length and temperature distribution. The model also shows the ability of capturing the instant when the fluid pressure begins to oscillate after the heat load is supplied, which is a fundamental information for the correct design of the engineering model that will be tested on the ISS. We also reveal the existence of strong liquid temperature gradients near the ends of liquid plugs both experimentally and by simulation. Finally, a theoretical prediction of the stable functioning of a large diameter PHP in microgravity is given. Results show that the system provided with an input power of 185W should be able to reach the steady state after 1min and maintain a stable operation from then on.