Mechanically assisted crevice corrosion (MACC) is a complication that may occur in vivo at modular metal interfaces following metal-on-polyethylene (MoP) total hip arthroplasty (THA). Metal ions released in vivo may be associated with adverse local tissue reactions (ALTR). While there is no definitive value, high serum ion levels are implicated as contributors to ALTR, and various screening levels have been recommended. The purpose of this investigation was to evaluate the relationship between synovial fluid (SF) cobalt and chromium ion levels and the risk of developing ALTR. This was a retrospective cohort study of 552 patients who underwent 621 MoP primary THAs. A total of 69 patients underwent revision THA due to symptomatic primary failure with elevated serum metal ions levels. There were 28 who had preoperative serum and intraoperative SF chromium and cobalt samples. Patient demographics, surgical, and laboratory data were collected. Descriptive statistics, Mann-Whitney U, Analysis of Variance (ANOVA) tests, and linear regression analyses were performed. There were 40.6% of revisions that had preoperative serum and intraoperative SF samples. The mean time to revision was 5.7 (range, 3.8 to 7.6) years. Mean SF cobalt and chromium levels were 870.9mcg/L (range, 1.1 to 8,300.0) and 573.5mcg/L (range, 1.3 to 10,000.0). Mean serum and SF cobalt-chromium ratios were 4.0 (range, 0.9 to 7.1) and 6.4 (range, 0 to 15.1), respectively. Elevated serum cobalt levels were predictive of ALTR (P = 0.002), SF levels were not. Analysis of preoperative serum to SF cobalt-chromium ratios showed poor correlation (R2 = 0.05). There was no correlation between SF ion levels and ALTR. Also, serum and intraarticular ion levels did not correlate, and SF levels did not provide additional value over serum levels for diagnosis or prognosis of MACC. Further studies are needed to better understand the relationship between serum and SF ion levels and its relationship to ALTR.