This study is a prospective double-blind randomized controlled trial to evaluate the effect of extended oral TXA after primary total TKA on short-term and mid-term postoperative outcomes, including function, pain, and postoperative complications over a 24-month period, with evaluations at 6 weeks, 3 months, 12 months, and 24 months. Each group of 175 patients will receive either extended oral TXA 1.95g daily or placebo for 7 days postoperatively. Function will be assessed by Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR) scores measured at all post operative time points as well as range of motion (ROM) (measured at all visits).

Inclusion Criteria:

• Patients are candidates for elective primary total knee arthroplasty.
• Patients ≥18 years of age
• Patients have been medically evaluated and scheduled for primary total knee arthroplasty.
• Patients undergo primary total knee arthroplasty with spinal anesthesia
• Patients receive 1g IV TXA prior to incision and 1g IV TXA at closure
• Patients are prescribed aspirin 81mg twice a day for postoperative VTE prophylaxis

Exclusion Criteria:

• Patients with an allergy to TXA
• Patients taking a preoperative anticoagulant other than aspirin
• Patients with a history of VTE
• Patients with chronic kidney disease
• Patients with active malignancy
• Current use of combined hormonal contraception (pill, patch, or ring)
• eGFR <60 mL/min/1.73 m² or other clinically significant renal impairment
• Use of Factor IX complex concentrates, anti-inhibitor coagulant concentrates, or all-trans retinoic acid (tretinoin)
• Anticipated need for tissue plasminogen activator (tPA) during the 7-day dosing period
• Individuals who are pregnant or breastfeeding, have a positive pre operative pregnancy test, or plan pregnancy during the 7 day dosing window. Women of childbearing potential must have a negative pre operative pregnancy test and use effective contraception through postoperative day . Individuals who are on hormonal contraceptives or hormone replacement therapies, with the exception of Progestin, are to be excluded.

The de-identified participant data from the final research dataset will be shared upon reasonable request beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Daniel.waren@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Daniel.waren@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.