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The present study explores net carbon-neutral road transport options in the EU27 in 2050 from a well-to-wheel (WtW) perspective. To this aim, three scenarios have been developed regarding the evolution of the road vehicle fleet composition in terms of the degree of electrification of powertrains, and technical measures such as vehicle efficiency improvements, transport flow, and transport volumes have been considered. The fleet scenarios are further combined with four scenarios deploying different mixes of alternative fuels in 2050, including electricity, e-fuels, liquid/gaseous advanced biofuels and remaining fossil fuel components. Two different electricity production pathways are considered, as well, one of them assuming fully renewable electricity production, and an alternative one including residual shares of nuclear and natural gas power plants plus carbon capture and storage. The Joint Research Centre's DIONE model was used for the scenario calculations. From a tank-to-wheel (TtW) perspective, each scenario reduces energy consumption, mainly due to powertrain electrification, with EU27 TtW road vehicle energy consumption in 2050 ranging from roughly 650 to 1650 TWh, which is 20%–53% of that of 2019. For the most strongly electrified fleet scenario with optimistic assumptions on measures to improve vehicle efficiency, transport flow and transport volumes and renewable electricity production, well-to-tank (WtT) energy consumption is around 110–160 TWh, depending on the fuel scenario. If a moderately electrified fleet is propelled with e-fuels, even when assuming fully renewable electricity and optimistic measures, the WtT energy consumption increases ten times or more, to 1300 TWh (2150 TWh with pessimistic measures). The results show that fleet electrification is the strongest lever for WtW transport energy consumption reduction among the options considered. Other efficiency measures contribute significantly to energy savings, but their benefit decreases with increasing fleet electrification. The production pathways of fuels make a substantial difference for WtW fleet energy requirement if the fleet is moderately electrified, in which case e-fuels require significant amounts of additional renewable electricity. Nevertheless, fuel production pathways become irrelevant from an energetic point of view under very ambitious electrification scenarios since fuel volumes become marginal. The economic feasibility and the societal acceptability of different pathways towards WtW carbon-neutrality of road transport is out of scope of this paper and requires further investigation. • The study examines well-to-wheel scenarios for 2050 carbon neutral road transport. • Electrification is the strongest driver in transport energy consumption reduction. • Vehicle efficiency and activity impacts decrease with fleet electrification. • With high fleet electrification fuel production barely impacts energy consumption. • E-fuels require particularly large amounts of additional renewable electricity. [ABSTRACT FROM AUTHOR]