The Energy Independence and Security Act of 2007 requires the U.S. to use 36 billion gallons of renewable fuel per year by 2022. Domestic ethanol production has increased steadily in recent years, growing from less than 5 billion gallons per year (bgpy) in 2006 to over 13 bgpy in 2010. While there is interest in developing non-oxygenated renewable fuels for use in conventional vehicles as well as interest in expanding flex-fuel vehicle (FFV) production for increased E85 use, there remains concern that EISA compliance will require further use of oxygenated biofuels in conventional vehicles. The Environmental Protection Agency (EPA) recently granted partial approval to a waiver allowing the use of E15 in 2001 and newer light-duty vehicles. Despite EPA's determination that E15 will not contribute to increases in full-useful life emissions in these vehicles, there remains concern amongst some vehicle manufacturers that the vehicle malfunction indicator light (MIL) may be displayed (or activated) due to increased use of oxygenates in gasoline. Similar concerns also exist for isobutanol and isopentanol, which are emerging as potential blending components for future gasoline formulations. This paper describes a test program in which increasing amounts of ethanol were added to gasoline to gradually increase the long term fuel trim (LTFT) until the MIL was displayed. When the MIL was activated, the threshold LTFT was recorded. Vehicles used in the MIL study were also used in the recently completed Department of Energy Catalyst Study (during which they were exposed to ethanol blends up to E20). No incidence of fuel-related MILs occurred during the 2 year catalyst aging program on the 86 vehicles from six of the largest manufacturers (Chrysler, Ford, GM, Honda, Nissan, Toyota). In the current MIL study, vehicles were driven on a specified 4-day cycle with multiple cold starts, idles, and hot soaks. Ethanol levels were increased steadily until the MIL was activated. Estimates of the rate of increase of LTFT as the fuel oxygen content increased were also determined. LTFT MIL thresholds were determined to vary from 18% to 38%, with the rate of LTFT increasing between 4-5% for a 10% increase in the ethanol blend level (or 3.5% oxygen in the fuel). These data were utilized in combination with statistical data on LTFT variability and mean values determined by the CRC E-90 study to project an estimate of the MIL activation frequency for the vehicle models tested in this study when they are used with 10%, 15%, and 20% by volume ethanol blends, and for equivalent oxygen content in blends of butanol and pentanol. A sensitivity analysis was also conducted to examine the relative importance of the variables to the estimated MIL occurrence rates for each vehicle. The results show that some vehicles are likely to exhibit some MIL illumination events when using E10, while others are estimated to have few, if any, MILs illuminate with E20. In general, the estimated rate of MIL illumination increases as the ethanol blend fraction increases, although in some cases few, if any, MIL illuminations are predicted. The results show that the greatest frequency of MIL activation is expected for vehicle models that utilize an LTFT threshold of 20% or less for MIL activation.