This study was undertaken to examine macrophage response to polycarbonate-urethane, a proposed alternative material to polyethylene in acetabular components of total hip arthroplasty. Polyethylene wear debris from total joint replacements has been linked to osteolysis and implant lifespan. It has been shown in vitro, that polyethylene particles cleaned of endotoxin generate less of an inflammatory cytokine response than endotoxin bound particles. Comparative particle induced effects on implant fixation were tested using endotoxin free cross-linked ultra-high molecular weight polyethylene (x-UHMWPE) and polycarbonate-urethane (PCU) particles with and without intraperitoneal injection (IP) of lipopolysaccharide (LPS) using a Ti-alloy femoral intramedullary nail rat model. MicroCT and mechanical testing assessment of peri-implant bone indicated significantly less bone and lower fixation strength, respectively, when the implant was surrounded by xUHMWPE particles compared to PCU particles (with and without LPS IP). This indicates particles of PCU may be less disruptive to bone-implant fixation than x-UHMWPE in vivo, under both LPS free and challenged conditions.