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Gas-to-Liquids (GTL) is a liquid diesel fuel produced from natural gas, which may have certain attributes different from conventional ultra low sulfur diesel (ULSD). In this investigation, GTL, ULSD, and their blends of 20% and 50% GTL in ULSD were tested in an older Mercedes C Class (MY1999, Euro 2) and a newer Opel Astra (MY2006, Euro 4) diesel vehicle to evaluate the performance in terms of fuel consumption and emissions. Each vehicle was pre-conditioned on-road with one tank full of test fuel before actual testing in a chassis dynamometer facility. Both vehicles were calibrated for European emission standards and operation, and they were not re-calibrated for the fuel tests at Argonne National Laboratory (ANL). In the two-vehicle EPA FTP-75, US06, and Highway drive-cycle tests, the emissions of carbon dioxide on a per-mile basis (g/mi) from all GTL-containing fuels were significantly lower than those from the ULSD.