Background Various surgical meshes are used in the repair of inguinal hernia and are associated with numerous complications. Our main objective in this study was to determine whether a biologic hernia matrix is equivalent to polypropylene mesh in an open inguinal hernia repair using the Lichtenstein technique. Study Design A prospective, randomized, double-blinded, single-center trial was conducted to evaluate the efficacy of a biologic Inguinal Hernia Matrix (IHM; Cook Medical) compared with polypropylene (PP) mesh using Lichtenstein's inguinal hernia repair in a 3-year outcomes study. Patients were evaluated for recurrence and complications by a blinded surgeon at 2 weeks, 3 months, 6 months, and 1 year post procedure. Patient demographics, including comorbidities and nutrition status, were recorded. Intraoperative information including hernia type and location, procedure time, level of difficulty, degree of surgeon frustration, and surgical experience were collected. Results One hundred male patients provided informed consent and were randomized into the study in a 1:1 fashion. There were no significant differences in degree of difficulty and level of frustration between the 2 groups. At 1-year follow-up, 3 recurrences were diagnosed in the IHM group as compared with none in the PP group (p = 0.11). Persistent pain trended higher in the PP group (6% vs 4%). All 3 recurrences occurred in the direct inguinal hernia group and were performed by attendings in the first year post training (3 different attendings). No recurrences occurred in patients operated on by more senior surgeons. Conclusions The IHM hernioplasty compares favorably with PP mesh at 1-year follow-up with similar recurrence rates and complications. Surgeon experience appears to be a major factor affecting successful outcomes.