Following implant placement, a soft tissue barrier will form at the healing abutment connection called peri-implant mucosa. 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 accelerate 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 60 implants were placed in 30 patients (2 implants per patient, one in the test group and one in the control group). In the test sites, EMD was administered around the healing abutment before soft tissues were sutured. Soft tissue healing index (HI) and secondary endpoints (clinical, radiographic, and patientreported outcomes) were measured. Better outcomes were recorded in patients receiving EMD for all parameters. The present results support the use of EMD to improve and accelerate soft tissue wound healing around implants.