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This study aimed at elucidating the influence of insertion protocol and implant shoulder design on peri-implant soft tissue healing.One month after removal of all maxillary premolars in 12 minipigs, 4 implants were installed in each quadrant. According to implant shoulder design, 3 groups were established: 1) rough, 0.4 mm; 2) smooth, 3 mm; and 3) smooth, 0.4 mm. One quadrant was randomized to flapless insertion, and the other was used for flap surgery in each animal. Mucosa biopsies were retrieved 1, 2, 4, and 12 weeks after surgery and subjected to a leukocyte count as well as pangenomic gene expression analysis.Flapless surgery shortened the period of postsurgical inflammation as shown by the leukocyte count and induced early constructive remodeling as indicated by the microarray. Regarding design of the implant shoulder, leukocyte count values were lowest for group 3.Flapless surgery in combination with group 3 implants appears to enhance peri-implant soft tissue healing.