Background: First-generation highly cross-linked polyethylene liners have reduced the incidence of wear particle-induced osteolysis. However, failed acetabular liners have shown evidence of surface cracking, mechanical failure, and oxidative damage. This has led to the development of second-generation highly cross-linked polyethylene, which has improved wear and mechanical properties and resistance to oxidation in vitro. Owing to its recent introduction, there are no publications describing its clinical performance. Questions/purposes: We assessed early clinical wear of a second-generation highly cross-linked polyethylene liner and compared its clinical performance with the published results of hip simulator tests and with first-generation highly cross-linked polyethylene annealed liners. Patients and Methods: Twenty-one patients were enrolled in a prospective cohort study. Clinical outcome and femoral head penetration were measured for 19 patients at 6 months and 1 and 2 years postoperatively. Results: The median proximal head penetration was 0.009 mm and 0.024 mm at 1 and 2 years, respectively. The median two-dimensional (2-D) head penetration was 0.083 mm and 0.060 mm at 1 and 2 years, respectively. The median proximal wear rate between 1 and 2 years was 0.015 mm/year. Conclusions: The wear rate calculated was similar to the in vitro wear rate reported for this material; however, it was less than the detection threshold for this technique. Although longer followup is required for wear to reach a clinically quantifiable level, this low level of wear is encouraging for the future clinical performance of this material. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.