Following implant placement, at healing abutment connection, a soft tissue barrier defined peri-implant mucosa will form. The dimension of this anatomical structure seems to play a key role in maintaining long- term peri-implant and marginal bone level stability. In its early stages, soft tissue healing is a process involving many cellular and molecular events. Enamel Matrix Derivative (EMD) may improve and fasten soft tissue wound healing and inflammatory resolution. In the present split-mouth randomized clinical trial, EMD was used to influence the early phase of soft tissue healing around dental implants placed with a single-stage approach into a completely healed ridge. A total of sixty implants were inserted in thirty patients. In the test group, EMD was administered around the healing abutment before soft tissues were sutured. Soft tissue healing index (HI), together with secondary endpoints (clinical, radiographic and PROMs), was measured. Better outcomes were recorded in patients receiving EMD when considering all parameters. Data here presented supports the use of EMD improve and accelerate soft tissue wound healing around implants.