OBJECTIVES: The Medicare Comprehensive Care for Joint Replacement (CJR) bundled payment program will cover TKA services from admission to 90 days after discharge, prompting hospitals to consider potentially cost-saving interventions. This study compared total hospital costs for TKA with and without bupivacaine liposomal injectable suspension (BLIS) to manage postsurgical pain. METHODS: This descriptive analysis included Medicare patients who underwent primary TKA at the five hospitals in the Premier Database with the highest use of BLIS from 2013 to 2015 and controls without BLIS from the same hospitals from 2011 to 2015. Total hospital charges and costs for TKA were aggregated for patients in both study groups at each hospital; costs are estimated by Premier using hospital-specific and item-specific charge to cost ratios. Aggregate charge to cost ratios for TKA were then calculated and compared for both study groups at each hospital. RESULTS: The five hospitals included 3,359 TKA Medicare patients who received BLIS and 5,785 controls. Total hospital charges ranged from $33,000 to $83,556 with BLIS (mean $57,700) and $32,611 to $85,559 without BLIS (mean $60,990), while total hospital costs ranged from $12,638 to $19,712 (mean $16,387) and $14,077 to $20,418 (mean $17,210) with and without BLIS, respectively. Overall charge to cost ratios for TKA at each hospital ranged from 2.00 to 6.61 with BLIS (mean 3.67) and 2.00 to 6.08 without (mean 3.71). The difference in charge to cost ratios between the BLIS and controls groups at each hospital ranged from -0.1% to 9.9% (mean 5.3%); at one hospital, total charges were higher but total costs were lower with BLIS. CONCLUSIONS: An analysis of Premier chargemaster data indicated that total hospital charges and costs for TKA were lower when using BLIS to manage postsurgical pain, though differences noted between hospitals in charges, costs, and charge to cost ratios.