Ethanol use in vehicle fuel is increasing worldwide, but the potential cancer risk and ozone-related health consequences of a large-scale conversion from gasoline to ethanol have not been examined. Here, a nested global-through-urban air pollution/weather forecast model is combined with high-resolution future emission inventories, population data, and health effects data to examine the effect of converting from gasoline to E85 on cancer, mortality, and hospitalization in the United States as a whole and Los Angeles in particular. Under the base-case emission scenario derived, which accounted for projected improvements in gasoline and E85 vehicle emission controls, it was found that E85 (85% ethanol fuel, 15% gasoline) may increase ozone-related mortality, hospitalization, and asthma by about 9% in Los Angeles and 4% in the United States as a whole relative to 100% gasoline. Ozone increases in Los Angeles and the northeast were partially offset by decreases in the southeast. E85 also increased peroxyacetyl nitrate (PAN) in the U.S. but was estimated to cause little change in cancer risk. Due to its ozone effects, future E85 may be a greater overall public health risk than gasoline. However, because of the uncertainty in future emission regulations, it can be concluded with confidence only that E85 is unlikely to improve air quality over future gasoline vehicles. Unburned ethanol emissions from E85 may result in a global-scale source of acetaldehyde larger than that of direct emissions.