Six clinical trials (3 RCTs and 3 non-RCTs) were included in this meta-analysis to determine the mid-term comparative efficacy of highly cross-linked polyethylene (HXLPE) and conventional polyethylene (CP) following TKA for end-stage knee osteoarthritis (OA) patients. Outcomes of interest included prosthesis loosening, osteolysis, tibial polyethylene wear, and postoperative knee function. Results demonstrated that HXPLE and CP were comparable for all reported outcomes. Additional trials are needed to provide a larger, more robust sample of patients that evaluate outcomes over the long-term.