The present work aims at investigating the compatibility of antioxidant with biodiesel through the tribological assessment of a compression ignition engine. In this research work, 2,6-di-tert-butylphenol, a novel antioxidant, has been blended with clean Karanja oil methyl ester at the rate of 500 ppm. The compression ignition engine has been operated for 256 h of long-term durability tests in two different phases using clean Karanja biodiesel (KBD100) and 500 ppm antioxidant-blended clean Karanja biodiesel (KBD100@E). The study revealed that the compression ignition engine operated with KBD100@E fuel has exhibited low lubricating oil degradation when compared to clean Karanja biodiesel at same 256 h of operation. The long-term endurance test also showed that the kinematic viscosity, flash point and total base number of lubricating oil collected from KBD100@E-fueled engine were observed to lower than KPD100-fueled engine. Similarly, the wear metal concentrations were higher in lubricating oil of KPD100-fueled engine than that of antioxidant-added KBD fuel and diesel fuels. Furthermore, the surface roughness results also showed that the cylinder liner surface of KPD100-fueled engine was more smoothened compared to KBD100@E-fueled engine. The wear of piston rings was also noted to be more severe for KBD100-fueled engine when compared to diesel and KPD100@E-fueled engines. Finally, it has been concluded that the compression ignition engine life can be improved by the addition of antioxidant with biodiesel fuel.