Background: Optimization of surgical instrument trays improves efficiency and reduces cost. The purpose of this study is to assess the economic impact of optimizing orthopedic instrument trays at a tertiary medical center. Methods: Twenty-three independent orthopedic surgical instrument trays at a single academic hospital were reviewed from 2017 to 2018. Using Lean methodology, surgeons agreed upon the fewest number of instruments needed for each of the procedure trays. Instrument usage counts, cleaning times, room turnover times, tray weight, holes in tray wrapping, wet trays, and time invested to optimize each tray were tracked. Cost savings were calculated. Student's t-test was used to determine statistical significance, with P < .05 considered significant. Results: The mean instrument usage before and after Lean optimization was 23.4% and 54.2% (P < .0001). By Lean methods, 433 of 792 instruments (55%) were removed from 11 unique instrument trays (102 total trays), resulting in a reduction of 3520 instruments. Total weight reduction was 574.3 pounds (22%), ranging from 2.1-16.2 pounds per tray. The number of trays with wrapping holes decreased from 13 to 1 (P < .0001). The process of examining and removing instruments took an average of 7 minutes 35 seconds per tray. The calculated total annual savings was $270,976 (20% overall cost reduction). Conclusion: In addition to substantial cost savings, tray optimization decreases tray weights and cleaning times without negatively impacting turnover times. Lean methodology improves efficiency in instrument tray usage, and reduces hospital cost while encouraging surgeon and staff participation through continuous process improvement. Level of Evidence: Economic Quality Improvement, Level III.