The large and mega yachts market shows the increasing trend of “expedition capable” vessels cruising all around the globe, from Antarctica to the Arctic Circle, with the highest comfort standards. Within this frame, the accurate assessment of the seakeeping characteristics is essential for the successful design and eventually the adoption of a stabilization systems. In 2022, the International Standardization Organization (ISO) published the first edition of a set standards to quantify the overall level of comfort on large yachts. The procedure requires the calculation of the Effective Gravity Angle (EGA) and of the Motion Sickness Incidence (MSI) at five locations on the ship, in prescribed environmental conditions and in two different situations: yacht at anchor and in transit. The level of comfort is quantified by a number of stars that goes from one to five, the highest number of stars corresponding to the highest comfort. In the present paper, the application of the ISO guidelines on a large yacht is shown. The Response Amplitude Operators (RAO) are obtained by Hydrostar^® software, MSI and EGA are calculated in Matlab^®. The comfort level is quantified and shown as weighted value for all periods at different positions and at two speeds and the maximum wave height for the excellent seakeeping is identified.