This study investigates the cyclic deformation, fatigue behavior, and failure mechanisms for Ti-6Al-4V ELI (extra low interstitial) with and without mean strain/stress. Mean stress effects on fatigue behavior were studied using four strain ratios. Fatigue data generated was used to assess mean stress fatigue life prediction approaches, including stress-based methods such as Goodman, Gerber, Morrow, Walker and Kwofie; as well as strain-based models, such as Morrow, Smith-Watson-Topper, Walker, Kwofie, Ince-Glinka and a modified version of the Smith-Watson-Topper. The stress-based models did not yield reasonable results and data scatter was observed. The strain-based models offered better results, specifically the Morrow approach which provided more accurate fatigue life predictions. Fractography analysis determined that the influence of material defects on fatigue life had no major differences across all the strain ratios considered. Overall observations indicate that inclusions near the surface had great influence on the fatigue behavior.