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OBJECTIVE In this study, the authors report their experience performing outpatient minimally invasive transforaminal lumbar interbody fusion (miTLIF) in an ambulatory surgery center (ASC) with 2 years of follow-up data. METHODS Patients who underwent miTLIF at the authors’ ASC from January 2012 through August 2024 were identified. Registry data were analyzed for demographics, surgical data, complications, hospital transfers, readmissions/reoperations, and patient-reported outcomes (PROs). The PRO measures included the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain and leg pain, EQ-5D, and EuroQol visual analog scale (EQ-VAS). RESULTS A total of 485 patients underwent single-level miTLIF in the Semmes Murphey ASC during this time. Of these patients, 179 had been enrolled in the registry and are the subject of this report. Most patients (176 patients, 98.3%) were discharged within a few hours of surgery. The mean patient age was 54 (range 20–75) years. There were 97 females and 82 males. A total of 179 (100%) patients had 3-month follow-up data, 171 (95.5%) had 1-year follow-up data, and 160 (89.4%) had 2-year follow-up data. Preoperatively, the mean back pain NRS, leg pain NRS, ODI, EQ-5D, and EQ-VAS scores were 6.98, 6.52, 44.14, 0.56, and 63.33, respectively. By 3 months postoperatively, the mean back NRS, leg NRS, ODI, EQ-5D, and EQ-VAS scores improved to 2.40, 1.21, 19.37, 0.81, and 81.15, respectively. By 1-year postoperatively, the mean back NRS, leg NRS, ODI, EQ-5D, and EQ-VAS scores were 2.29, 1.62, 12.73, 0.86, and 81.41, respectively. By 2 years postoperatively, the mean back pain NRS, leg pain NRS, ODI, EQ-5D, and EQ-VAS scores were 2.86, 1.98, 13.87, 0.82, and 81.15, respectively. There were 3 durotomies (1.7%), all of which were treated with fibrin glue, and the patients were discharged within a few hours of surgery. One patient (0.56%) had a superficial surgical site infection that required oral antibiotics but no further surgery. One patient (0.56%) developed a postoperative hematoma. One patient (0.56%) was found to have a urinary tract infection postoperatively. There were 4 (2.2%) readmissions and 2 (1.1%) reoperations within 90 days. CONCLUSIONS This is the largest reported series of miTLIFs performed in a single ASC with 2 years of follow-up data. Patients showed significant improvement in a variety of validated PROMs. Complications, 90-day hospital readmissions, and reoperation rates were acceptably low. For carefully selected patients, ASC-based miTLIF appears to be safe, durable, and highly effective.