In the present paper, results of an experimental investigation carried out in a modern diesel engine running at different operating conditions and fuelled with blends of gasoline–diesel and n-butanol–diesel, are reported. The exploration strategy was focused on the management of injection pressure and timing to achieve a condition in which the whole amount of fuel was delivered before ignition. The aim of the paper is to evaluate the effects of fuel blends, which have low cetane number (CN) and are more resistant to auto-ignition than diesel fuel, on performance and engine-out emissions. Blends were mixed by the baseline diesel (D00) with 40% of commercial unleaded gasoline (G40) and 40% of n-butanol (B40). Fuel consumption and engine-out gaseous and smoke emissions from fuel blends were measured and compared to the neat diesel fuel. The investigation was performed on a turbocharged, water-cooled, direct-injection diesel engine, equipped with a common-rail injection system. The engine equipment included an exhaust gas recirculation system controlled by an external driver, a piezo-quartz pressure transducer to detect the in-cylinder pressure signal and a current probe to acquire the energizing current to the injectors. Engine tests were carried out at two engine operating conditions: 2000 r/min at 0.5 MPa and 2500 r/min at 0.8 MPa brake mean effective pressure, exploring the effect of start of injection, O2 concentration at intake and injection pressure on combustion behaviour and engine-out emissions. Taking advantages of the higher resistance of G40 and B40 to auto-ignition, it was possible to extend the range in which a partial premixed combustion was achieved. The management of injection pressure, O2 concentration at intake and injection timing allowed partial premixed combustion to be obtained by extending the ignition delay, both for diesel fuel and blends. The longer ignition delay and the better mixing before combustion made more advanced injection timings, which reduced smoke and nitrogen oxide emissions, possible. The joint effect of higher resistance to auto-ignition and higher volatility of n-butanol and gasoline improved the emissions of the blends compared to the neat diesel fuel, with a low penalty on fuel consumption.