INTRODUCTION: Evidence-based enhanced surgical recovery (ESR) programs integrate a multidimensional approach to optimize patients during the pre-, intra-, and post-operative phases of surgery. Smaller studies suggest benefits of ESR in spine surgery, but large-scale evidence is lacking. METHODS: In this retrospective case-control study of a healthcare system ESR program, data from thoracolumbar (TL) fusions were extracted from electronic medical records. Patients were divided into two cohorts, ESR or non-ESR, based upon enrollment into an ESR program defined by (1) preoperative patient education, (2) multimodal analgesia, (3) intraoperative fluid optimization, (4) opioid-sparing anesthesia, and (5) early postoperative nutrition and ambulation. Exclusion criteria were: unknown ESR status, age <18 yrs, and surgery for tumor, infection, or trauma. Impact of ESR upon postoperative daily morphine milligram equivalents (MME), length of hospital stay (LOS), and 30-day hospital readmission rates (READMIT) was evaluated for single-level TL fusions, multi-level TL fusions, and all TL fusions using regression models. RESULTS: 51,236 TL fusion cases were identified from 2018 to 2021: 24,391 participated in an ESR program and 26,845 did not. ESR and non-ESR groups were demographically similar. For single level TL fusions, ESR was associated with decreased MME (β= -8.76, p < 0.001), LOS (β= -8.85, p < 0.001), and READMIT (OR = 0.77, 95% CI: 0.67-0.88). For multi-level TL fusions, ESR was associated with decreased MME (β = -7.32, p < 0.001) and LOS (β= -12.14, p < 0.001), and for all TL fusions, ESR was associated with decreased MME (β= -7.94, p<0.001), LOS (β = -10.54, p < 0.001), and READMIT (OR = 0.91, 95% CI: 0.84-0.98). CONCLUSIONS: This national healthcare system analysis of 51,236 TL fusion cases by 1,352 surgeons at 138 centers confirms that ESR adoption is associated with decreased MME, LOS, and READMIT. Surgeons should consider adoption of ESR programs to improve patient care.