The diagnosis of periprosthetic joint infection (PJI) in patients with failed metal-on-metal (MoM) bearings and corrosion reactions in hip arthroplasties can be particularly difficult, because the clinical presentation of adverse local tissue reactions may mimic that of PJI, because it can also occur concurrently with PJI, and because common laboratory tests used to diagnose PJI may be elevated in patients with MoM THAs. We sought to determine the test properties of the serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial fluid white blood cell (WBC) count, and synovial fluid differential (percent polymorphonuclear cells [PMNs]) in diagnosing PJI in either MoM hips undergoing revision for a variety of indications or in non-MoM hips undergoing revision for either corrosion reaction or full-thickness wear. Additionally, we sought to describe how MoM bearings, metal debris, and corrosion reactions can confound the analysis of the synovial fluid WBC count and affect its diagnostic use for PJI. We reviewed 150 revision hips meeting specified inclusion criteria (92 MoM total hips, 19 MoM hip resurfacings, 30 non-MoM bearings with corrosion, and nine full-thickness bearing surface wear with metallosis). In our review, we diagnosed 19 patients as infected using Musculoskeletal Infection Society (MSIS) criteria. Mean laboratory values were compared between infected and not infected patients and receiver operator characteristic curves were generated with an area under the curve (AUC) to determine test performance and optimal cutoffs. After excluding the inaccurate synovial fluid samples, the synovial fluid WBC count (performed accurately in 102 patients) was the best test for the diagnosis of PJI (AUC=98%, optimal cutoff 4350 WBC/μL) followed by the differential (performed accurately in 102 patients; AUC=90%, optimal cutoff 85% PMN). The ESR (performed in 131 patients) and CRP (performed in 129 patients) both had good sensitivity (83% and 94%, respectively). Patients meeting MSIS criteria for PJI had higher mean serum ESR, CRP, synovial fluid WBC count, and differential than those not meeting MSIS criteria (p<0.05 for all). An observer blinded to the MSIS diagnosis of the patient assessed the synovial fluid samples for inaccuracy secondary to metal or cellular debris. Synovial fluid sample "inaccuracy" was defined as the laboratory technician noting the presence of metal or amorpous material, fragmented cells, or clots, or the sample having some defect preventing an automated cell count from being performed. Of the 141 patients who had a synovial fluid sample initially available for review, 47 (33%) had a synovial fluid sample deemed to be inaccurate. A synovial fluid WBC count was still reported; however, 35 of these 47 hips (75%) and 11 of these 35 (31%) were falsely positive for infection. The diagnosis of PJI is extremely difficult in patients with MoM bearings or corrosion and the synovial fluid WBC count can frequently be falsely positive and should be relied on only if a manual count is done and if a differential can be performed. A more aggressive approach to preoperative evaluation for PJI is recommended in these patients to allow for careful evaluation of the synovial fluid specimen, the integration of synovial fluid culture results, and repeat aspiration if necessary. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.