The experimental research reported in this paper evaluates the potential of blends consisting of different biomass derived alcohols and vegetable oils as possible drop-in components in fossil Diesel fuel to overcome the need for modifications in engine hardware or calibration settings. Two C-8-alcohols (n-octanol and its isomer 2-ethylhexanol) and two C-10-alcohols (n-decanol and its isomer 2-propylheptanol) were blended with hydrotreated vegetable oil (HVO), rapeseed methyl ester (RME) and fossil Diesel. The blends were prepared to mimic the properties of standard Diesel fuel, in particular the cetane number was held constant. The percentage of fossil Diesel in the blends was 0%, 10% or 20%. The impact of the fuel composition on performance and emissions in a Volvo D13 single cylinder heavy duty research engine operated with standard engine settings was analyzed. Experiments revealed that the engine performance with the different blend compositions resembled that with standard Diesel with regard to the indicated thermal efficiency. Owing to the lower heating value of the fuel blends, the specific fuel consumption of the blends was about 6% higher than that of Diesel. Emissions were found to be similar among all alcohol-HVO blends. Compared to Diesel emissions, a reduction of carbon monoxide was measured for the blends. The yields of HC and NOx did not vary significantly for the different fuel blends. Soot emissions were substantially lower compared to those obtained with neat Diesel fuel. The lowest soot emissions were achieved with the fully renewable fuel composition, which did not contain any aromatic structures. Evaluation of the particle size distribution showed that the number of particles in agglomeration mode was substantially higher for standard Diesel fuel than for the blends. Alcohol-HVO-blends particle sizes were mainly in the nucleation mode range. Overall, the obtained results indicate that blends mainly containing long-chain alcohols could be a potential replacement for fossil Diesel fuel.