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In this research, gasoline engine performance and emission characteristics were studied when powered by diisopropyl ether-gasoline blends. The main objective of this study is to determine the behavior of diisopropyl ether-gasoline blends at various engine speeds and compression ratios. Further, the engine parameters were optimized using the response surface methodology. Enriched oxygen, higher latent heat of vaporization, and the readily volatile nature of the fuel enhanced the brake thermal efficiency and lowered the hydrocarbons and carbon monoxide due to a better combustion rate. The developed model exhibited superior R2 values with a 0.957 desirability factor. The optimum parameters such as speed, compression ratio, and fuel-blend concentrations were found at 2250 rpm, 10:1, and D25 (75% gasoline and 25% diisopropyl ether), respectively. The responses for the optimal input parameters were brake thermal efficiency (31.53%), specific fuel consumption (0.2923 kg/kWh), carbon monoxide (0.14% by Vol.), hydrocarbons (31 ppm), and oxides of nitrogen (708 ppm). The predicted values for optimum engine parameters were validated with the experimental data, and their percentage of absolute error was found to be less than 5%. Thus, the study concludes that diisopropyl-ether gasoline blends can be used as an alternative fuel to enhance the brake thermal efficiency and reduce the pollution level, and the proposed numerical model can predict the responses with high accuracy. [ABSTRACT FROM AUTHOR]