The aim of the present split-mouth prospective study was to evaluate clinically and histologically the bone regeneration obtained following preprosthetic vertical bone augmentation performed with titanium-reinforced dense polytetrafluoroethylene membrane (d-PM) compared to titanium mesh (TM). Healthy adult patients presenting with bilateral partial edentulism in the posterior mandible requiring vertical ridge augmentation for implant placement purposes were consecutively included. One side of the mandible was randomly assigned to the use of d-PM, the other to TM. The graft consisted in a mixture of autogenous bone harvested nearby the surgical site and deproteinized bovine bone mineral particles in a 1:1 ratio. On each side during bone augmentation surgery, a 2-mm diameter mini-implant was inserted for clinical and histological analyses. After a healing period of 8 months, the second surgical phase was carried out to remove the nonresorbable barriers, to evaluate clinically the vertical bone gain, and to collect a bone biopsy that included the mini-implant. During the same surgical session, dental implants were inserted in a prosthetically guided position. A total of five patients were enrolled. Eight out of 10 sites healed uneventfully. In the remaining two sites, premature exposure of the TM was observed. Mean vertical bone gain of 4.2 and 1.5 mm was achieved in d-PM and TM groups, respectively (p = 0.06). A mean mineralized tissue of 48.28 and 35.54% was observed in d-PM and TM groups, respectively (p = 0.51). The vertical bone gain, although not significantly, was higher in the d-PM group. Similar histological outcomes were noticed if exposure did not occur. In case of wound dehiscence, major resorption was observed. Both d-PM and TM can be used to augment atrophic localized ridges vertically. The outcome of bone regeneration seems to be impaired by exposure of the device. How to cite this article: Maiorana C, Fontana F, Rasia dal Polo M, et al. Dense Polytetrafluoroethylene Membrane versus Titanium Mesh in Vertical Ridge Augmentation: Clinical and Histological Results of a Split-mouth Prospective Study. J Contemp Dent Pract 2021;22(5):465-472.