This paper investigates the performance characteristics and workability of high reclaimed asphalt pavement (RAP) mixtures in the presence of a bio-modified binder. Accordingly mixtures with high percentages of RAP were designed with and without bio-modification to examine whether bio-modification can facilitate the incorporation of RAP. The bio-modification was performed by modifying a virgin asphalt binder with a bio-binder produced from swine manure. The four mixtures that were designed and evaluated were a control mixture incorporating virgin materials, the control mixture incorporating 40% RAP, the control mixture incorporating the bio-modified binder, and the control mixture incorporating the bio-modified binder and 40% RAP. The effect of the bio-modified binder on the stiffness and workability of the control mixture with and without RAP was evaluated by measuring the dynamic modulus and the torque resistance of the mixtures, respectively. The performance of each mixture was evaluated for fatigue cracking (overlay tester) and moisture susceptibility/rutting potential (Hamburg wheel-tracking device). Finally, the degree of blending between the virgin and RAP binders was evaluated for each mixture. The data indicated that the addition of the bio-modified binder helped reduce the stiffness of the control mixture with 40% RAP to a level closer to the stiffness of the same mixture without RAP. In addition, the presence of the bio-binder led to improving the workability of the mixtures, especially this was very evident at high-RAP content of 40%. The data indicated that the bio-modified binder improved the fatigue properties and cracking characteristics and had no negative effect on the moisture susceptibility/rutting characteristics of the control mixture with 40% RAP. Overall, data indicated that there was a good degree of blending between the virgin/bio-modified and RAP binders.