Recent evidence showing that computer-assisted total knee arthroplasty (TKA) is associated with better outcomes compared with conventional TKA for patients with end-stage knee osteoarthritis has not been included in economic evaluations of computer-assisted TKA, which are needed to support coverage decisions. This study evaluated the cost-effectiveness of computer-assisted TKA from a payer's perspective, incorporating recent evidence. We compared computer-assisted TKA with conventional TKA with regard to costs (in 2022 U.S. dollars) and quality-adjusted life-years (QALYs) using Markov models for elderly patients (≥65 years of age) and patients who were not elderly (55 to 64 years of age). Costs and QALYs were estimated in the lifetime for elderly patients and in the short term for patients who were not elderly, under a bundled payment program and a Fee-for-Service program. Transition probabilities, costs, and QALYs were retrieved from the literature, a national knee arthroplasty registry, and the National Center for Health Statistics. Threshold and probabilistic sensitivity analyses were conducted to examine the robustness of key estimates used in the base-case analysis. Using projected estimates of TKA utilization, the total cost savings of performing computer-assisted TKA rather than conventional TKA were estimated. Compared with conventional TKA, computer-assisted TKA was associated with higher QALYs and lower costs for both elderly patients and patients who were not elderly, regardless of payment programs, making computer-assisted TKA a favorable treatment option. Widespread adoption of computer-assisted TKA in all U.S. patients would result in an estimated total cost saving of $1 billion for payers. Compared with conventional TKA, computer-assisted TKA reduces costs to payers while providing favorable outcomes. Payers may consider providing additional payment incentives to providers for performing computer-assisted TKA, to achieve outcome improvement and cost control by facilitating widespread adoption of computer-assisted TKA. Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.