Objective: The aim of the present study is to compare the temporal surface volume coefficient obtained in the cadaveric model from subdermal and supraperiosteal injections to the clinical setting when treating temporal hollowing. Material and Methods: A total of 36 subjects were included in this investigation, 17 patients (16 females, 1 male; 46.3 ± 8.9 years; 25.5 ± 2.8 kg/m2) and 19 cadaveric specimens (11 females, 8 males; 76.4 ± 11.5 years; 24.0 ± 5.1 kg/m2). Subdermal and supraperiosteal injections were performed and live subjects were evaluated and followed for 12 months. The surface volume coefficients were calculated using 3D surface volume scanning and compared for validity. Results: No statistically significant difference was detected between the clinical outcome scores of the subdermal vs supraperiosteal injection technique. The supraperiosteal injection technique utilized significantly more product 1.20 ± 0.5 cc [range: 0.50 – 2.6 cc] compared to the subdermal 0.71 ± 0.2 cc [range: 0.30 – 1.20 cc] vs with P< 0.001. This difference was consistent with the different values of the cadaveric surface volume coefficient (subdermal vs supraperiosteal): 1.00 ± 0.2 vs 0.70 ± 0.2. At 12-month follow-up, the product loss was 19% for the subdermal injection and 21% for patients treated with supraperiosteal injections. Conclusion: The results of the study support the clinical validity of the surface volume coefficient. They demonstrate that the different injection volumes necessary to deliver aesthetically appealing results when utilizing the subdermal vs the supraperiosteal technique can be explained by the region-specific surface volume coefficient. J Drugs Dermatol. 2019;18(6):533-540.