Surgical sutures have different sizes, structures, whereas they are being used for various surgeries. The high friction performance of surgical sutures in the suturing process may cause inflammation and pain, leading to a longer recovery time. This paper presents an understanding of the tribological behavior of surgical suture with monofilament and multifilament structures, by means of a penetration friction apparatus (PFA). The results indicated that structure and surface topography of the surgical suture had a pronounced effect on the tribological interactions. It was found that the friction force and abrasion area of skin substitute with the penetration of polyglycolic acid (PGA) multifilament surgical suture were larger than that of Nylon monofilament surgical suture. Meanwhile, more abrasion at the pull-in boundary of skin substitute was observed compared with that at the pull-out boundary.