BACKGROUND/AIM: Synovial calprotectin has been demonstrated as a promising biomarker for periprosthetic joint infections (PJI) in painful total hip (THA) and knee arthroplasties (TKA). However, its diagnostic utility has not been evaluated explicitly in cases with marked loosening or migration of the implant. Concerns have already been raised in cases with metallosis and severe periprosthetic osteolysis because wear-induced inflammation may yield false positive results. The purpose of this study was to evaluate calprotectin for the diagnosis of PJI in cases that preoperatively demonstrate moderate to severe periprosthetic osteolysis or implant migration as signs for implant loosening in THA and TKA. PATIENTS AND METHODS: Thirty-three patients were included in this prospective study between February of 2019 and November of 2021. The extent of osteolysis was classified according to Engh et al., Paprosky et al., and the modern Knee Society Radiographic Evaluation and Scoring System. Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin using a lateral-flow-assay were tested against the European Bone and Joint Infection Society (EBJIS) definition for PJI. Statistic quality criteria were calculated and compared using a binary classification test. RESULTS: Ten patients were classified as confirmed infections according to the EBJIS definition (7 THA and 5 TKA). The calprotectin assay yielded a sensitivity of 0.60, a specificity of 0.61, a positive predictive value of 0.40, and a negative predictive value of 0.78. The calprotectin assay resulted in nine false positive and four false negative cases. No correlation between the extent of osteolysis and false classification by means of the calprotectin assay was observed. CONCLUSION: The diagnostic accuracy of synovial calprotectin is impaired if moderate to severe signs of implant loosening are present. If PJI is unlikely, the calprotectin LFT can be applied as a further exclusion tool as the negative predictive value remains relatively high.