Abstract This work studies the impact of using n-butanol or ethanol in blends with diesel fuel (extenders) on combustion, cyclic irregularity, and exhaust emissions trade-off (balance). Experiments were conducted at two speeds and three loads in a fully-instrumented, six-cylinder, four-stroke, heavy-duty direct injection (HDDI), turbocharged, ‘Mercedes-Benz’ bus diesel engine. Measured combustion chamber pressures and their heat release rate diagrams provide motivating features of the combustion process. Since low-ignition quality fuels as ethanol and n-butanol may instigate unstable engine operation, this work centers also into the examination of cyclic combustion variations (irregularity) strength as mirrored in the cylinder pressure diagrams, by analyzing for maximum pressures and mean effective pressures, employing statistical analysis tools for averages and coefficients of variation. The n-butanol or ethanol diesel fuel blends present stronger cyclic variations than the corresponding neat diesel fuel cases, with the ethanol ones being a bit stronger for the same value of fuel-bound oxygen. The above results and the different physical and chemical properties of biofuels assist the elucidation of engine stability differences, as well as the balance of all measured regulated exhaust emissions: smoke, nitrogen oxides (NOx), carbon monoxide (CO), and unburned hydrocarbons (HC). Defeat of smoke-NOx and CO-HC adverse trade-offs is revealed.