Hydrogen mobility embodies a promising solution to address the challenges posed by traditional fossil-fuel-based vehicles. The use of hydrogen in small heavy duty road vehicles based on internal combustion engines (ICEs) may be appealing for two fundamental reasons: direct electrification seems less promising in heavy duty transport systems and fuel cell-based hydrogen vehicles implementation may not proceed at the expected pace due to higher investment costs compared to ICEs. On the other hand, hydrogen combustion is gaining attractiveness and relies on robust and cheap technologies, but it is not the only renewable solution. In this framework, this work presents a methodology to assess Weel-to-Whell primary energy consumption and CO2 emissions of small heavy-duty vehicles. The methodology is applied in a real case-study, namely a passenger coach travelling on a 100 km-mission in non-optimized conditions. Therefore, the suitability of hydrogen is compared with standard diesel and other alternative diesel-type fuels (biodiesel and synthetic diesel types). Hydrogen shows competitivity with standard diesel from the point of view of CO2 emission reduction (-29%) while it hides a higher primary energy consumption (+40%). Nonetheless, HVO brings the highest benefits both from the point of view of primary energy consumption and emission reduction, namely -35% and 464-634 kgCO2/100km avoided compared to hydrogen.