Hydrotreated vegetable oil (HVO) diesel fuel is a promising biofuel candidate that can complement or substitute traditional diesel fuel in engines. It has been already reported that by changing the fuel from conventional EN590 diesel to HVO decreases exhaust emissions. However, as the fuels have certain chemical and physical differences, it is clear that the full advantage of HVO cannot be realized unless the engine is optimized for the new fuel. In this article, we studied how much exhaust emissions can be reduced by adjusting engine parameters for HVO. The results indicate that, with all the studied loads (50%, 75%, and 100%), particulate mass and NOx can both be reduced over 25% by engine parameter adjustments. Further, the emission reduction was even higher when the target for adjusting engine parameters was to exclusively reduce either particulates or NOx. In addition to particulate mass, different indicators of particulate emissions were also compared. These indicators included filter smoke number (FSN), total particle number, total particle surface area, and geometric mean diameter of the emitted particle size distribution. As a result of this comparison, a linear correlation between FSN and total particulate surface area at low FSN region was found.