Recently, corrosion at the head-neck junction in metal-on-polyethylene bearing total hip arthroplasty (THA) has been recognized as a cause of adverse local tissue reactions (ALTR). Serum metal levels have been advocated as a tool for the diagnosis of ALTR, however no prior studies have specifically examined their utility. The purpose of this study was to determine the optimal cut-off values for serum cobalt and chromium in diagnosing ALTR after metal-on-polyethylene bearing THA. We reviewed 447 consecutive patients with serum metal levels tested at our institution and identified 62 with a metal-on-polyethylene bearing who had axial imaging or underwent reoperation to confirm the presence or absence of ALTR. Receiver operating characteristic curves were produced to identify cut-off thresholds to optimize sensitivity and diagnostic test performance was characterized. 42 Of the 62 patients (66%) were positive for an ALTR. The best test for the diagnosis of ALTR was the serum cobalt level (area under the curve [AUC]=99%). A threshold cut-off of ≥ 1.0 ng/ml had a sensitivity of 100%, specificity of 90%, positive predictive value (PPV) of 96%, and negative predictive value (NPV) of 100%. Serum chromium levels were also diagnostic (AUC=87%). A threshold cut-off of ≥ 0.15 ng/ml had a sensitivity of 100%, specificity of 50%, PPV of 81%, and NPV of 100%. Finally, serum cobalt to chromium ratio was also helpful for diagnosis (AUC=90%). A threshold cut-off of 1.4 for the cobalt to chromium ratio offered a sensitivity of 93%, specificity of 70%, PPV of 87%, and NPV of 82%. Measurement of serum cobalt with a threshold value of 1.0 ng/ml in our experience is the best test for identifying the presence of ALTR in patients with a metal-on-polyethylene THA. Measurement of chromium and the ratio of cobalt to chromium are also of value.