The designers of two-wheeled motorcycles, in the phase of setting up a new project, have the need to carry out ergonomic evaluations on both the pilot and the passenger, from which the optimal comfort and control conditions will arise during the future use of the vehicle. Commonly, the most used method is based on the previous experience of the manufacturer and on the comparison with the choices made by the competitors. This article describes a methodology developed in collaboration with the Italian motorcycle brand Aprilia, owned by Piaggio & C., a company world leader in the sector, designed for the setup phase of new vehicles. The method provides a flexible tool, starting from the Enduro segment and for the different users’ body size (expressed in percentiles). The analysis was done on five commercial Enduro motorcycles from different leading competitor manufacturers. The authors used a mixed method based on numerical and experimental data, detected on virtual models, and on report cards made by professional testers. The results have been showed and discussed.