This article presents our research results on the physical-chemical and direct injection diesel engine performance parameters when fueled by pure diesel fuel and retail hydrotreated vegetable oil (HVO). This fuel is called NexBTL by NESTE, and this renewable fuel blends with a diesel fuel known as Pro Diesel. A wide range of pure diesel fuel and NexBTL100 blends have been tested and analyzed: pure diesel fuel, pure NexBTL, NexBTL10, NexBTL20, NexBTL30, NexBTL40, NexBTL50, NexBTL70 and NexBTL85. The energy, pollution and in-cylinder parameters were analyzed under medium engine speed (n = 2000 and n = 2500 rpm) and brake torque load regimes (30–120 Nm). AVL BOOST software was used to analyze the heat release characteristics. The analysis of brake specific fuel consumption showed controversial results due to the lower density of NexBTL. The mass fuel consumption decreased by up to 4%, and the volumetric consumption increased by up to approximately 6%. At the same time, the brake thermal efficiency mainly increased by approximately 0.5–1.4%. CO, CO2, NOx, HC and SM were analyzed, and the change in CO was negligible when increasing NexBTL in the fuel blend. Higher SM reduction was achieved while increasing the percentage of NexBTL in the blends.