Objective: To characterize whether medical comorbidity predicts persistent moderate-severe pain after total hip arthroplasty (THA). Methods: We analyzed the prospectively collected data from the Mayo Clinic Total Joint Registry for patients who underwent primary or revision THA between 1993 and 2005. Using multivariable-adjusted logistic regression analyses, we examined whether certain medical comorbidities were associated with persistent moderate-severe hip pain 2 or 5 years after primary or revision THA. Odds ratios (ORs), along with 95% confidence intervals (CIs) and P value, are presented. Results: The primary THA cohort consisted of 5,707 THAs and 3,289 THAs at 2 and 5 years, and revision THA, 2,687 and 1,627 THAs, respectively. In multivariable-adjusted logistic regression models, in the primary THA cohort, renal disease was associated with lower odds of moderate-severe hip pain (OR 0.6; 95% CI 0.3, 1.0) at 2 years. None of the comorbidities were significantly associated at 5 years. In the revision THA cohort, heart disease was significantly associated with higher risk (OR 1.7; 95% CI 1.1, 2.6) at 2 years and connective tissue disease with lower risk (OR 0.5; 95% CI 0.3, 0.9) of moderate-severe hip pain at 5-year follow-up. Conclusion: This study identified new correlates of moderate-severe hip pain after primary or revision THA, a much-feared outcome of hip arthroplasty. Patients with these comorbidities should be informed regarding the risk of moderate-severe index hip pain, so that they can have a fully informed consent and realistic expectations. © 2013 American Academy of Pain Medicine Wiley Periodicals, Inc.