This paper presents the validation process for the structural layer coefficient determined mechanistically for high polymer (HP) asphalt mixtures (i.e., 0.54) through full-scale laboratory testing of asphalt pavements. Two instrumented full-scale pavement experiments were conducted in the PaveBox setup at the University of Nevada, Reno. A flexible pavement structure with a conventional polymer-modified asphalt layer was evaluated in Experiment No. 1. Meanwhile, a flexible pavement structure with a reduced-thickness HP asphalt concrete (AC) layer was evaluated in Experiment No. 2. Similar vertical surface deflections (except under the center of the applied surface load), higher vertical stresses at the middle of the base layer, and similar vertical stresses below the subgrade surface were observed with the reduced thickness of the HP AC layer. Moreover, better overall fatigue and rutting performance in the AC layer, slightly higher rut depths in the unbound layers, and similar total rut depths were observed by means of mechanistic analysis with the use of HP AC pavement. In general, the results and findings of this study supported the selection of 0.54.