Ethanol has long been regarded as the optimal gasoline-alternative biofuel for spark-ignition (SI) engines. It is used widely in Latin and North America and is increasingly accepted as an attractive option across Europe. Nevertheless, its low energy density requires a high rate of manufacture; in areas which are deficient of arable land, such rates might prove problematic. Therefore, fuels with higher calorific values, such as butanol or 2,5-dimethylfuran (DMF) deserve consideration; a similar yield to ethanol, in theory, would require much less land. This report addresses the suitability of DMF, to meet the needs as a biofuel substitute for gasoline in SI engines, using ethanol as the biofuel benchmark. Specific attention is given to the sensitivity of DMF to various engine control parameters: combustion phasing (ignition timing), injection timing, relative air-fuel ratio and valve timing (intake and exhaust). Focus is given to the window for optimization; the parameter range which sustains optimal IMEP (within 2%) but provides the largest reduction of emissions (HC or NO). The test results using a single-cylinder SI research engine at 1500 rpm show how DMF is less sensitive to key engine parameters, compared to gasoline. This allows a wider window for emissions optimization because the IMEP remains optimal across a greater parameter range.