Abstract Background Of late, periarticular analgesic injection (PAI) has become a common alternative treatment for pain following total hip arthroplasty (THA). However, the systemic effects of PAI containing corticosteroids in patients subjected to THA have not been investigated. This study evaluated the analgesic efficacy and systemic effects of PAI containing a corticosteroid in patients subjected to THA. Methods This single-center, retrospective cohort study enrolled patients undergoing unilateral, primary THA. A total of 197 patients (200 hips) were included in the final analyses, with 87 hips in the PAI group and 113 hips in the control group. Numeric Rating Scale (NRS) and laboratory data were assessed preoperatively and on postoperative days (POD) 1 and 7. Pearson’s correlation coefficients were obtained to assess the correlations between the D-dimer level on POD 7 and each outcome measure on POD 1. Results The postoperative white blood cell count (WBC) was significantly higher in the PAI group than in the control group. Postoperative NRS, creatine phosphokinase (CK), and C-reactive protein (CRP) levels were significantly lower in the PAI group. D-dimer levels were significantly lower in the PAI group on POD 7. Postoperative aspartate transaminase (AST), alanine aminotransferase, blood urea nitrogen, and creatinine levels were within reference ranges. D-dimer levels on POD 7 showed a significant negative correlation with WBC on POD 1 (r=-0.4652) and a significant positive correlation with the NRS score and AST, CK, CRP, and D-dimer levels on POD 1 (r = 0.1558, 0.2353, 0.2718, 0.3545, and 0.3359, respectively). Conclusions PAI containing a corticosteroid may be an effective treatment for pain and inflammation after THA, and it does not seem to cause drug-induced liver or kidney injury. Moreover, corticosteroid PAI can may accelerate early ambulation, which prevents the elevation of postoperative D-dimer levels, and may reduce the risk of deep venous thrombosis.