Within the cluster of excellence “Tailor-Made Fuels from Biomass” at the RWTH Aachen University, two novel biogenic fuels, namely 1-octanol and its isomer dibutyl ether (DBE), were identified and extensively analyzed in respect of their suitability for Diesel engine combustion. Both biofuels feature very different properties, especially regarding their ignitability. In previous works of the research cluster, promising synthesis routes with excellent yields for both fuels were found, using lignocellulosic biomass as source material. Both fuels were investigated as pure components in optical and thermodynamic single cylinder engines. For 1-octanol at lower part load, almost no soot emission could be measured, while with DBE the soot emissions were only about a quarter of that with conventional Diesel fuel. At high part load, the soot reduction of 1-octanol was more than 50% and for DBE more than 80 % respectively. Based on these promising initial results, this paper will report about additional experimental investigations that were initiated to exploit the complete potential of both advanced biofuels in terms of emissions and efficiency. A single cylinder research engine was utilized and the engine calibration was optimized using design of experiments at lower and higher part load. At high part load, it was possible to increase the efficiency by more than one percent compared to the base calibration in the same load point. Furthermore, the already low soot emissions of both biofuels compared to Diesel fuel could also be further halved compared to the base calibration. In a last step reported here, a sensitivity analysis was performed in order to validate the previously built models and to get further insight into the influence of the single calibration parameters on engine performance.