Periprosthetic osteolysis is often nonsymptomatic and hard to visualize by conventional radiography. Cross-linked N-telopeptide of type I collagen (NTx), a marker of osteoclast mediated bone resorption, has been suggested to evaluate local particulate-induced osteolysis in patients operated on with a total hip prosthesis. Urine specimens were sampled after hip joint replacement in 160 patients. NTx was analyzed by a commercially available ELISA kit. Osteolysis was identified in the acetabulum and confirmed at operation. Using analysis of covariance to correct for differences in age, gender, and time after operation, NTx (mean SD) was 36+/-12 BCE/nM creatinine in patients with osteolysis (n=33) and 27+/-13 BCE/nM creatinine in patients without osteolysis (n=127) (p=0.003). Eighteen hips of 38 (47%), demonstrating an annual wear of more than 0.2 mm and an NTx value above 29 BCE/nM creatinine, had been revised due to osteolysis. The osteolysis prevalence in this group was increased 10 times (CI 4-23, p< 0.05). Indeed, NTx release and annual wear were both associated with increased prevalence of osteolysis, however, independently of each other. NTx seems a feasible marker of periprosthetic osteolysis. A preoperative baseline NTx level is likely needed for its use as a predictor of periprosthetic osteolysis in individual cases.