Deviation of volumetric properties of asphalt mixtures, such as voids in mineral aggregates (VMA), from the agency–specified thresholds can cause minor to significant changes in pavement performance. This paper presents the results of the study on the effects of the deficiency of VMA parameters (ΔVMADesign) on the fatigue performance of asphalt pavements. Dynamic modulus and fatigue tests were performed on two types of mixtures (one with 9.5-mm nominal maximum aggregate size (NMAS) and the second one with 19-mm NMAS) at three levels of ΔVMADesign. The results were analyzed using two simulation models (i.e., FlexPAVE 1.1Alpha and AASHTOWare Pavement ME Design version 2.3.0 (Pavement ME)). The results showed that fatigue service life reduction was linearly correlated to an increase in ΔVMADesign and could reach almost 50 % for a pavement with ΔVMADesign of 3 %. Additionally, while both Pavement ME and FlexPAVE showed comparable results in terms of top-down cracking/damage predictions, the results of the analysis performed by FlexPAVE in terms of bottom-up damage prediction were more consistent with respect to the expected behavior of pavement structure in terms of damage.