The most important long-term complication in total joint replacements is aseptic osteolysis. Wear particles such as polyethylene (PE) debris are considered to be one of the causes that play a central role. Several studies indicated that PE can be visualised in paraffin-embedded tissue sections not only by polarised light, but also after oil red staining. To determine whether oil red staining enables sensitive detection of PE, we examined staining of mechanically-produced PE particles by oil red. Furthermore, we studied oil red staining of paraffin-embedded tissue specimens of patients with failed uncemented and cemented total knee and hip prostheses. We applied double labelling of sections by immunohistochemistry using the macrophage marker anti-CD68 and oil red staining. We found that oil red stains both isolated PE particles and PE particles in paraffin-embedded tissue sections. Polymethylmethacrylate particles in failed cemented arthroplasties did not stain in paraffin sections. Double labelling showed strong colocalisation of CD68 and PE. We suggest that oil red staining is a sensitive method to detect PE particles. Oil red staining is particularly helpful in these cases which show a characteristic histological feature of aseptic prosthesis loosening without particles being detectable with routine microscopy and polarised light. We also established that immunohistochemical methods can be applied together with the oil red staining method.