Their easy availability, lower well-to-wheel emissions, and relative ease of use with existing engine technologies have made ethanol and ethanol-gasoline blends a viable alternative to gasoline for use in spark-ignition (SI) engines. The lower energy density of ethanol and ethanol-gasoline blends, however, results in higher volumetric fuel consumption compared with gasoline. Also, the higher latent heat of vaporization can result in cold-start issues with higher-level ethanol blends. On the other hand, a higher octane number, which indicates resistance to knock and potentially enables more optimal combustion phasing, results in better engine efficiency, especially at higher loads.This paper compares the fuel consumption and emissions of two ethanol blends (E50 and E85) with those for gasoline when used in conventional (non-hybrid) and power-split-type plug-in hybrid electric vehicles (PHEVs). Engine-in-the-loop (EIL) test results from a previous study of an E85-series PHEV show about 4% lower fuel energy consumption than gasoline because of better engine efficiency at high loads. In a conventional vehicle, the decrease in fuel energy consumption when gasoline is compared with E85 is less than 1%.The series PHEV operates as an electric vehicle when in charge-depleting (CD) mode. For the power-split PHEV, the CD mode of operation has multiple, but infrequent, “engine on” events, resulting in different engine utilization than the series PHEV. Differences in the hybridization configuration also result in different regions of operation for the engine in the CD, as well as the charge-sustaining (CS), mode of operation. The vehicle control strategy for a particular configuration remains the same for the different fuel blends.For the power-split PHEV, we assess the sensitivity of fuel consumption and emissions to the three fuels using EIL testing and compare them with EIL results for a series PHEV and a conventional vehicle. We propose changes to the PHEV control strategy to optimize the vehicle system for each fuel blend and configuration.