Autogenous soft tissue augmentation procedures around natural teeth and dental implants are performed daily by clinicians. However, patient morbidity is often associated with the second surgical site; hence, research is moving toward an era where matrices may substitute autogenous grafts. The aim of this study was to assess the soft tissue response to a collagen matrix in an animal model. Nine pigs were included in this study. Each animal received four collagen matrices, two for each mandible. Three cohorts were included in the study: group A, where the matrix was applied as an onlay on a partial-thickness flap; group B, where the matrix was inserted under a partial-thickness flap; and group C, where the matrix was inserted in an inverted position under a full-thickness flap. Sacrifice occurred at 7, 15, and 30 days postoperatively for histologic assessment. The collagen matrix was seen in place for the first 2 weeks, and it was completely replaced by healthy connective tissue within 30 days in the inlay cohorts. No inflammatory adverse reactions were noticed in any specimen, resulting in optimal integration of the device. This study showed an optimal integration within 30 days postoperative of the placement of experimental collagen matrix in the soft tissues of an animal model. Its proven safety in this model provides an optimal starting point for further research projects considering its clinical applications.