Turbocharging, increasing the compression ratio, and downsizing a spark-ignition engine are well known strategies for improving vehicle fuel economy. However, such strategies increase the likelihood of engine knock due to higher in-cylinder pressures and temperatures. A high octane fuel, such as E85, effectively suppresses knock but is not necessary in most parts of the engine operating map. To better utilize a high octane fuel, dual fuel injection has been suggested where high octane fuel is injected only when the engine is about to knock. However, the effects of downsizing, retarding spark timing, and increasing compression ratio on dual fuel applications are not well understood. To investigate these questions, GT-power simulations along with engine experiments and engine-in-vehicle simulations for a passenger vehicle and a medium-duty truck were conducted. First, engine performance maps for various boosts, compression ratios, and spark retards were created, with lines of constant fuel RON superposed. Then, parametric studies were conducted to analyze the effects of cylinder volume/boost level, spark retard, and compression ratio on the vehicle fuel consumption, ethanol usage, and the average engine efficiency. Downsizing a naturally-aspirated engine by 50% resulted in about a 30% increase in fuel economy. Ethanol consumption varied from 5 to 40% (by volume) of the total fuel used, depending on the details. Moderate amounts of spark retard reduced ethanol consumption by half while not deteriorating fuel economy by much. Increasing compression ratio above 11.5 had a marginal return in fuel economy while demanding a significantly larger amount of ethanol.