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Background: Enhanced recovery after surgery (ERAS) protocols have demonstrated success in reducing hospital stay and opioid consumption, but are less well studied in patients undergoing tissue expander-based breast reconstruction (TEBR). This study evaluates the effectiveness of an ERAS postoperative protocol for TEBR at a high-volume center., Methods: All patients undergoing immediate tissue expander reconstruction after the introduction of ERAS were prospectively included from April 2019 to June 2023. An equivalent number of similar patients were retrospectively reviewed before this date as the non-ERAS control. Data included demographics, operative details, postoperative length of stay, inpatient and discharge narcotic quantities, inpatient pain assessments, postoperative radiation, and complications within 90 days., Results: There were 201 patients in each cohort with statistically similar demographics. Patients in the ERAS cohort were more likely to undergo prepectoral reconstruction (83.1% versus 4.5%, P < 0.001), be discharged by day 1 (96.5% versus 70.2%, P < 0.001) and consume lower inpatient milligram morphine equivalent (MME) median (79.8 versus 151.8, P < 0.001). Seroma rates (17.4% versus 3.5%, P < 0.001) and hematoma incidence (4.5% versus 0%, P = 0.004) were higher in the ERAS cohort. Adjusting for implant location, ERAS was associated with a 60.7 MME reduction (β=-60.7, P < 0.001) and a shorter inpatient duration by 0.4 days (β =-0.4, P < 0.001). Additionally, prepectoral reconstruction significantly decreased MME (β=-30.9, P = 0.015) and was the sole predictor of seroma development (odds ratio = 5.2, P = 0.009)., Conclusions: ERAS protocols significantly reduce opioid use and hospital stay after TEBR., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)