The study was carried out to evaluate the efficacy of a xenogeneic CM when used as a soft tissue substitute in the reconstruction of an adequate amount (at least 2 mm) of keratinized tissue around dental implants. The xenogeneic CMs have already been investigated in order to check their compatibility and effectiveness as scaffold [19, 20]. One of the first studies was conducted by Schoo and Coppes, who experimented the capacities of a freeze-dried dura mater grafting material in stimulating keratinized mucosa, with very poor results [21]. Two studies by Harris, in 2001, analyzed the usefulness of acellular dermal matrices when positioned upon the periosteum and bone [22, 23], without any particular results. Furthermore, in 2001, Wei P. and Laurell L. conducted two studies: one clinical and one histological [24]. Six patients received an autologous graft while the remaining six an allogeneic one. The increment in adherent mucosa was detectable in both groups, but the gain was very little with the allogeneic graft. This was related to an excessive shrinkage of the graft post-operatively. Histologically, it was observed that all grafted sites showed a scar-like tissue, incapable of inducing cellular differentiation. The fast resorption represented a big concern in this technique leading to a disturbed healing and sequentially to a lack of keratinized tissue. Harris et al. underlined the great esthetic outcome in addition to the efficacy of substitutive matrices for soft tissue [25]. Despite the physical and mechanical characteristics of these matrices are still under investigation, it has already been observed how these matrices show statistically significant results confronted with the autologous grafting techniques [26]. Comparable results were observed evaluating not only by keratinized mucosa and thickness and vestibular depth evaluation but also by histological study [27]: during the first week of healing, it has been noticed a tissue remodeling due to phagocytosis of pre-existing collagen fibers by macrophages. After 2 weeks, new collagen fibers were detected as long as neoangiogenesis and re-epithelization on the membrane surface. At 4 weeks, it was difficult to find pre-existing collagen fibers. At 10 weeks, the healing process was complete and the esthetic is already acceptable. Schmitt et al. achieved similar outcomes in their study, which compared free gingival grafts and a porcine CM [16]. At 90 days after surgery, biopsies were harvested for histologic and immunohistologic analyses. It was observed the presence of specific keratinized tissue markers is in the CM grafted areas. CMs were also clinically tested as an alternative option for root coverage. McGuire and Scheyer tested the CM associated to a coronally advanced flap in recession defects [28]. They find out how the porcine CM in combination with a coronal flap represented a satisfactory alternative to autografts for covering dehiscence-type recession defects. They also noticed a reduction of the morbidity due to the absence of soft tissue graft harvesting. Nevins M. et al. tested the porcine CM around a single tooth [11]. After 1 year from surgery, both xenogeneic and autologous grafts healed perfectly, showing mature connective tissue and the presence of enough keratinized mucosa. The author underlined the better esthetic outcome of the CM, which was showing a perfect tissue integration. Herford et al. investigated the efficacy of CMs for keratinized mucosa augmentation in cases of lack [29]. They demonstrated an overall mean shrinkage of 14% (range, 5 to 20%). Sanz et al. confirmed how xenogeneic CMs guarantee predictable and satisfactory results: their primary endpoint was to evaluate the potentiality in gaining keratinized tissue in comparison with an autologous graft [16]. At 6 months, they observed an insignificant statistical variance between the autologous (60% shrinkage) and the xenogeneic (67%). Despite the CM shrinkage range is still very wide (from 14 to 75%), most of the authors observed that the majority of shrinkage occurred in the first month after surgery. In the present study, the highest shrinkage rate was observed in the first 6 months (P = 0.002) while the following follow-up at 1, 4, and 5 years. The shrinkage was slower but reached a final value of 59%, which is included in the range observed in the other studies. In the present paper, by analyzing the post-operative course, one factor is particularly highlighted: the great decrease in morbidity. Post-operative pain in autologous grafting is caused by the presence of a second surgical site, the donor site. Most of the patients who underwent this type surgery did not feel any pain at all, except a little nuisance that required a mild analgesic as medication. In the present study, the grafts were additionally covered with a vestibular retention splint. The use of the vestibular retention splint guaranteed a mechanic protection for the grafts. Moreover, it had a preventive effect on reinsertion of vestibular muscle fibers. Despite the influence of the splint on the width of keratinized mucosa has not be taken in consideration in this study, Heberer et al. previously concluded its use after vestibuloplasty reduced the graft shrinkage [30]. Furthermore, they observed a general reduction of time of the surgery and post-op morbidity too. The CM is extremely easy to use, with an average length of surgery of 30 min, excluding anesthesia [16]. Intra-operative and post-operative bleeding was extremely limited. The xenogeneic CM showed an ideal haemostatic effect with no excessive bleeding during surgery and no bleeding at all during post-operative period, similar to other techniques using absorbable collagen sponges in different kinds of treatments [31]. Furthermore, all grafted sites presented, when healing was completed, an optimal integration with the surrounding tissues, as stated by other authors in previous studies [15,16,17]. Rotundo an Pini-Prato observed the good esthetic of the CM also when used in the coverage of multiple gingival recession [32]. Laino et al. described excellent results of CM in wound repairing when placed after intraoral mucosal biopsy [33]. Recently, Schmitt et al. observed the long-term efficacy of CM when used in vestibuloplasty when compared to free gingival graft [34]. Despite the free gingival group showed lower values of keratinized tissue resorption, the CM showed good stability and better esthetic outcomes. Further studies with a larger sample, investigating the long-term effectiveness of CMs and alternative treatment options, should be performed in the future to better assess a univocal outcome about the topic.