<p>Ti6Al4V ELI titanium alloy is one of the most widely used damage tolerance alloys in the field of aerospace. Fracture toughness is an important damage tolerant parameter, on which stringent requirements are imposed in many application scenarios. To broaden its application field, more sufficient study on this alloy is in need. This paper focuses on exploring the fracture resistance of Ti6Al4V ELI alloy with a industrially prevalent air-cooled microstructure and analyzing the various influencing factors related to it. Crack propagation path tortuosity has been deemed as an important factor influencing fracture toughness. However, the EBSD results show that crystallographic orientation of lamellar α has limited influence on the crack propagation path. Meanwhile, the measured crack path tortuosity showed a weak consistency with the variation trend of fracture toughness. In addition, seven types of fractal dimensions studied in present work have no obvious correlation with fracture toughness. This is mainly due to the nature of the fractal dimension which is a measure of the irregularity of complex forms. By considering the influence of phase constitution on the fracture resistance of Ti6Al4V ELI alloy, a composite fracture toughness prediction model corresponding to different microstructure types was built and then verified. This model shows good prediction accuracy for Widmanstatten microstructure as well as equiaxed/bimodal microstructure, for which the prediction error is all within 13.3%.</p>