Abstract E85 (85 vol% ethanol and 15 vol% gasoline blend) is one of the most promising sustainable fuels for SI engines, thanks to the optimum trade-off between pollutant emissions and cost of implementation, starting from a pure gasoline baseline. From the point of view of engine performance, the most relevant differences from such a baseline are related to the heat of vaporization and to the laminar flame speed. The higher heat of vaporization helps to reduce combustion temperature, thus the risk of knocking, but it also slows down the air-mixing process; the small amount of Oxygen in the fuel molecule leads to a slightly different combustion behavior. The goal of this study is to compare commercial gasoline (E5, 5 vol% ethanol and 95 vol% gasoline blend) and E85, by means of CFD 1D (GT-Power) and 3D (AVL-FIRE) simulations, using experimentally calibrated models. The reference engine is a single-cylinder, four-stroke, PFI motorcycle unit, with a displacement of 463 cc and a maximum power > 30 kW at 9500 rpm. After the calibration, carried out on the E5 version, the fuel type is changed to E85 in the 1D model, in order to provide accurate Initial Conditions (ICs) and Boundary Conditions (BNDs) to the CFD-3D analysis. Then, a series of combustion simulations are carried out at maximum power operative point (9500 rpm – WOT), varying spark advance and equivalence ratios. Results reveal that an increase of fuel flow rate and a new calibration of spark timing are needed when the engine runs on E85 to reach performances comparable to the ones obtained with E5. Simulations also show that, moving from E5 to E85, combustion efficiency can be significantly increased, with a small reduction in engine performance. An estimation of specific emissions, provided by ECFM-3Z combustion model, show that, using E85, CO and HC emissions can be significantly reduced with a small increase of NO emissions, compared to gasoline case.