BACKGROUND Despite increased experience and technical developments in total knee arthroplasty (TKA), chronic postsurgical pain (CPSP) remains one of physicians' biggest challenges. The aim of the present study was to evaluate the effectiveness of perineural injection therapy (PIT) in the management of CPSP after TKA. MATERIAL AND METHODS A total of 60 patients who had been surgically treated with TKA because of advanced knee osteoarthritis was included in the present study. The study included 2 groups. Group A consisted of patients who received 3 rounds of PIT combined with standard postoperative TKA protocol during the same period. Group B received standard postoperative TKA protocols (rehabilitation programs, oral and intravenous analgesics). Clinical effectiveness was evaluated via Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Scale (VAS) at baseline and 1-, 3-, and 6-month follow-ups. RESULTS All repeated measures showed significant improvements (P<0.001) in both groups for VAS and WOMAC scores. These scores were significantly better in group A in all follow-up periods compared with group B (P<0.001). Twenty-nine patients (93.5%) in group A reported excellent or good outcomes compared with 26 patients (89.6%) in group B. CONCLUSIONS PIT is a promising approach in CPSP with minimal cost, simple and secure injection procedures, minimal side effects, and higher clinical efficacy.