This study investigated the clinical effect of topical application of tranexamic acid (TXA) in arthroscopic synovectomy of pigmented villonodular synovitis (PVNS) of the knee. Eighty patients who were diagnosed with unilateral knee PVNS underwent arthroscopic synovectomies from January 2017 to January 2021 and were retrospectively investigated in this study. Patients were divided into two groups: group A was the control group, whereas patients in group B received an intra-articular injection of 50 mL of TXA (1 g:100 mL) immediately after the synovectomies. The primary outcome measurement was the drainage volume of the affected knee in each postoperative stage, as well as the hematological parameters. Secondary outcomes included visual analog scale score, knee range of motion, and Lysholm score. Postoperative complications were also recorded. A lower volume of drainage was found in group B than in group A on postoperative day (POD) 1, on POD 2, and in total (POD 1, P =.000; POD 2, P =.000; total, P =.000). A lower visual analog scale pain score in group B was noticed on POD 1 ( P =.000) and POD 2 ( P =.005). Range of motion ( P =.019) and Lysholm score ( P =.001) were significantly superior in group B compared with group A on POD 14. Regarding complications, 3 patients in group A and 1 patient in group B developed deep venous thrombosis after surgery. Hematomas were found intra-articularly in 5 patients in group A during follow-up. Intraarticular topical application of TXA was effective in reducing postoperative bleeding and early postoperative pain for patients who underwent arthroscopic synovectomy of PVNS. [ Orthopedics . 2023;46(3):e179–e185.]