Although at present nonabsorbable meshes are the preferred material for tension-free hernioplasty, some problems with their use have yet to be addressed (i.e., chronic pain and infections). In order to address these disadvantages, a collagen-based material, the porcine small-intestinal submucosa mesh (Surgisis Inguinal Hernia Matrix, Cook Surgical, Bloomington, IN, USA), has recently been developed for hernia repair. With the aim of investigating the clinical safety and effectiveness of Surgisis IHM inguinal hernia repair, we report our experience of 45 consecutive hernioplasties with a medium-term follow-up. The surgical technique for the use of this material in hernioplasty is described in detail. Although some local (i.e., seromas) and general (i.e., hyperpyrexia), complications appeared in the immediate postoperative period (all of them disappeared spontaneously), no rejection or infection was observed after operations. At the 2-year follow-up, a low degree of pain and discomfort and no recurrences were observed. We conclude that the Surgisis IHM hernioplasty is feasible with promising results and, from a clinical perspective, seems safe and effective.