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Ethanol based fuels have seen increased use in recent years due to their renewable nature as well as increased governmental regulatory mandates. While offering performance advantages over gasoline, especially at high compression ratios, these fuels are more sensitive to pre-ignition (PI). Pre-ignition experiments using ethanol (E100) and E85 were performed in a CFR spark ignition engine using a diesel glow plug “hot spot” to induce PI. PI is found to occur over a specific air-fuel ratio range based on hot spot temperature. Additionally, increasing ethanol content or compression ratio (CR) decreases glow plug temperature thresholds for PI. A kinetics-based model was used to simulate pre-ignition of E100 and to elucidate sensitivities of pre-ignition to various operating parameters, including initial charge temperature, air dilution, and residual dilution. The model shows that the most violent cases of PI can be mitigated by switching to either lean or rich operation.