Background Adverse local tissue reaction (ALTR) is not only a prominent cause of metal-on-metal (MoM) implant revision, but may also compromise the result of revision surgery. Patients treated with MoM arthroplasty and subsequently revised as a result of ALTR have been shown to experience worse patient-reported outcomes, inferior survivorship, and more complications when compared with patients receiving MoM implants who were revised for reasons other than ALTR. There is conflicting evidence as to whether the presence of symptoms is associated with ALTR in patients with MoM implants. Blood metal ions are associated with ALTR, but a consensus on appropriate thresholds associated with ALTR risk is lacking. Questions/purposes (1) Was the presence of symptoms as measured by patient-reported outcome measures associated with ALTR presence and severity as noted on metal artifact reduction sequence (MARS)-MRI in patients treated with one design of MoM THA or hip resurfacing arthroplasty (HRA)? (2) Could reliable thresholds for blood metal ion levels be determined that were associated with ALTR presence on MARS-MRI? Methods This retrospective study presents a secondary analysis of data drawn from a prospective, international, multicenter study of the recalled Articular Surface Replacement (ASR) hip system. This larger study aims to identify risk factors for revision and provide followup guidelines for the many unrevised ASR patients. A total of 1721 patients were enrolled from 16 centers in six countries after the device was recalled and are followed annually for 5 years. In the present analysis, data from the enrollment visit (mean time from index surgery, 7.5 years; SD 3.5 years) were considered. Only patients from two centers conducting MARS-MRI on all patients regardless of clinical presentation as a standard of care were included to avoid selection bias. A total of 327 unilateral patients fulfilled our inclusion criteria (90% of those eligible). The level of symptoms was systematically determined using the Harris hip score and a visual analog scale for pain, and whole blood metal ion levels were collected from all patients. MARS-MRIs were analyzed by a single reader for ALTR presence (Anderson classification), diameter, and synovial thickness. A validation series of 35 MARS-MRIs indicated excellent intrareader reproducibility of the evaluations (intraclass correlation = 0.82) and substantial agreement (κ coefficient = 0.64) was achieved between the MARS-MRI reader and a musculoskeletal radiologist with > 10 years of experience with MARS-MRI. Binary logistic regression was used to determine variables independently associated with ALTR. Receiver operator characteristic curves were used to determine sensitive and specific cut points for cobalt and chromium. Results After controlling for confounding variables, presence of symptoms was determined to be a risk factor for ALTR (odds ratio, 2.9; p = 0.007) in patients treated with ASR MoM THA. Moreover, among patients undergoing ASR MoM THA with ALTR, synovial thickness correlated with symptomaticity (p = 0.030). For patients undergoing ASR MoM HRA, we found no association between symptoms and ALTR prevalence or severity. A cobalt cutoff of 3.2 parts per billion (ppb) was associated with increased risk of ALTR (p < 0.001; sensitivity, 68%; specificity, 71%) in ASR MoM THA. In patients with ASR MoM HRA, a cobalt threshold of 2.9 ppb was indicative of ALTR (p < 0.001; sensitivity, 79%; specificity, 69%). Conclusions The risk factors identified in the current study may be used to stratify patients receiving MoM implants in terms of ALTR risk. We found that symptoms are associated with an increased likelihood of ALTR presence in ASR MoM THA and that cobalt ion level is associated with ALTR in ASR MoM THA as well as ASR MoM HRA. Importantly, MoM HRA followup protocols that exempt asymptomatic patients from annual followup are not justified because asymptomatic patients are no less likely to have ALTR than symptomatic patients. Blood metal ion levels may reliably be used to screen patients undergoing MoM HRA. For patients undergoing MoM THA, a combination of symptom state and blood metal ion levels may be used to determine ALTR risk. Level of Evidence Level III, diagnostic study.