The objective of this paper is to analyze the performance and the combustion of a large-bore medium-speed engine running with hydro-treated vegetable oil (HVO) at low engine load. This fuel has a paraffinic chemical structure and high cetane number (CN). The main benefits are thus lower emission compared to diesel fuel and low soot values. The facility used in this study is a research engine, where the conditions before and after the machine, the valve timing and the injection parameters are fully adjustable. Several in-cylinder conditions before the combustion have been tested. The results are promising and show the benefits of HVO compared to diesel fuel. In fact, it has been possible to reduce nitrogen oxides (NOx) emission over 50% running with HVO and opportunely tuned valve timing.