BackgroundCare pathways are increasingly important as the shift toward value-based care continues; however, there is an inconsistent literature regarding their efficacy. The authors hypothesized that a total knee arthroplasty (TKA) care pathway, at a multihospital health system, would decrease cost, length of stay (LOS), discharges to inpatient facilities, postoperative complications at 90 days, and improve patient experience. MethodsA historical control study with multivariable regression was used to determine the association of an evidence-based care pathway with episode of care cost, LOS, discharge disposition, 90-day postoperative complications, and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores. ResultsIn total, 6760 primary TKA surgeries were analyzed. Multivariable regression demonstrated that the full protocol period was associated with a decrease in episode of care costs (−8.501%, 95% confidence interval [CI] −9.639 to −7.350), a decrease in LOS (−26.966%, 95% CI −28.516 to −25.382), and an increase in discharges to home (odds ratio [OR] 3.838, 95% CI 3.318-4.446). The full protocol was not associated with a change in 90-day complications (OR 1.067, 95% CI 0.905-1.258) or patient willingness to recommend (OR 1.06, 95% CI 0.72-1.55). Adjusted episode of care cost savings, normalized to average national Medicare reimbursement, were $2360 per patient. ConclusionTKA care pathways are an effective tool for standardizing care and reducing costs across a large health system. Further investigations are needed to develop interventions to consistently reduce complications. National scale implementation of care pathways in TKA could lead to estimated cost reductions of approximately $1.6 billion annually.