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Background: The use of tranexamic acid (TXA) has become widespread in orthopedics to promote hemostasis and has been successfully used to reduce blood loss and infection risk in joint arthroplasty. However, the cost effectiveness of routine TXA use for the prevention of periprosthetic infections in total shoulder arthroplasty remains unknown., Methods: The acquisition cost of TXA ($5.22) for our institution, along with values from the literature for the average cost of infection-related care ($55,243) and the baseline infection rates for patients without TXA use (0.70%),were used to perform a break-even analysis. The absolute risk reduction (ARR) of infection necessary to justify the prophylactic use of TXA in shoulder arthroplasty was calculated from the nontreated and break-even infection rates., Results: TXA is considered cost-effective if it prevents one infection out of 10,583 total shoulder arthroplasty's (ARR = 0.009%). It is economically justifiable with an ARR range of 0.001% at a cost of $0.50/g to 0.181% at $100/g. At varying costs of infection-related care ($10,000-$100,000) and varying baseline infection rates (0.50%-8.00%) and routine use of TXA remained cost-effective., Conclusion: The use of TXA is an economically viable practice for infection prevention following shoulder arthroplasty if it reduces the infection rate by 0.009%. Future, prospective studies should be conducted to observe whether TXA reduces the infection rate by more than 0.009%, showing cost effectiveness., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)