Tranexamic acid (TXA) is an anti-fibrinolytic agent that has been shown to decrease blood loss and transfusion requirements during hip and knee replacements. The purpose of this Doctorate Nursing Practice (DNP) Scholarly Project is to develop and evaluate a clinical practice guideline (CPG) for the safe and efficacious administration of TXA in hip and knee arthroplasty. A CPG was created and revised with the aid of a multi-disciplinary subject matter expert (MSME) group. The DNP students presented a draft of the CPG along with graded evidence based on current literature to the stakeholders on the team. Following the meeting, an online version of the AGREE II Instrument was distributed to the MSME group to critique and appraise the CPG. The AGREE II tool was designed to evaluate the methodological rigor in guideline development. Following the AGREE II analysis and revisions to the CPG, the guideline was approved by the Chief Anesthesiologist at the institution and was presented to the entire anesthesia department for future implementation. Following this presentation, the Practitioner Feedback Questionnaire (PFQ) was distributed and collected in an anonymous manner. The PFQ analysis revealed that 100% of the end users agreed that there is a strong need for the CPG; however, it was noted that 9% of the end users strongly disagreed that the CPG would be used in their practice. New practice guidelines frequently experience resistance to change by end-users. Further end-user clinical development should focus on educating staff on evidence-based practice as the literature continues to expand.