<p>The pterygopalatine fossa (PPF) is a deep, anatomically complex midfacial space that serves as a major neurovascular crossroads. Owing to its confined boundaries and multidirectional communications, it is difficult to visualize using conventional teaching materials. This study aimed to develop a physically enlarged negative-space three-dimensional (3D) printed model of the PPF and to evaluate its impact on anatomical comprehension. A three-dimensional (3D) digital model of the pterygopalatine fossa was developed using pre-existing digital bone models obtained from a commercial repository and refined using ZBrush software, ensuring reproducibility of the modeling workflow. A negative-space representation of the fossa was created and scaled to twice its anatomical size. The model was exported in STL format and printed using acrylonitrile butadiene styrene (ABS) filament. Internal neurovascular structures were represented using color-coded materials. Fifty-two third-year dental students were divided into a theoretical instruction group (<i>n</i> = 27) and a 3D model group (<i>n</i> = 25). Pre- and post-instruction assessments were performed, and within- and between-group comparisons were analyzed using paired and independent t-tests. Both groups demonstrated significant improvement in post-test scores (<i>p</i> &lt; 0.001). However, the mean score increase was significantly greater in the 3D model group (3.96 ± 2.47) compared with the theoretical group (2.22 ± 1.60) (<i>p</i> = 0.004). The effect size for the difference in improvement between groups was large (Cohen’s d ≈ 0.84). The enlarged negative-space 3D printed model was associated with improved short-term anatomical understanding of the pterygopalatine fossa compared with conventional theoretical instruction. This reproducible and low-cost model may represent a useful adjunct in clinically oriented teaching of complex deep facial spaces.</p>