OBJECTIVE: There has been increasing interest in the use of spinal anesthesia (SA) for spine surgery, especially within Enhanced Recovery After Surgery (ERAS) protocols. Despite the wide adoption of SA by the orthopedic practices, it has not gained wide acceptance in lumbar spine surgery. Studies investigating SA versus general anesthesia (GA) in lumbar laminectomy and discectomy have found that SA reduces perioperative costs and leads to a reduction in analgesic use, as well as to shorter anesthesia and surgery time. The aim of this retrospective, case-control study was to compare the perioperative outcomes of patients who underwent minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF) after administration of SA with those who underwent MIS-TLIF under GA. METHODS: Overall, 40 consecutive patients who underwent MIS-TLIF by a single surgeon were analyzed; 20 patients received SA and 20 patients received GA. Procedure time, intraoperative adverse events, postoperative adverse events, postoperative length of stay, 3-hour postanesthesia care unit (PACU) numeric rating scale (NRS) pain score, opioid medication, and time to first ambulation were collected for each patient. RESULTS: The two groups were homogeneous for clinical characteristics. A decrease in total operating room (OR) time was found for patients who underwent MIS-TLIF after administration of SA, with a mean OR time of 156.5 ± 18.9 minutes versus 213.6 ± 47.4 minutes for patients who underwent MIS-TLIF under GA (p < 0.0001), a reduction of 27%. A decrease in total procedure time was also observed for SA versus GA (122 ± 16.7 minutes vs 175.2 ± 10 minutes; p < 0.0001). No significant differences were found in intraoperative and postoperative adverse events. There was a difference in the mean maximum NRS pain score during the first 3 hours in the PACU as patients who received SA reported a lower pain score compared with those who received GA (4.8 ± 3.5 vs 7.3 ± 2.7; p = 0.018). No significant difference was observed in morphine equivalents received by the two groups. A difference was also observed in the mean overall NRS pain score, with 2.4 ± 2.1 for the SA group versus 4.9 ± 2.3 for the GA group (p = 0.001). Patients who received SA had a shorter time to first ambulation compared with those who received GA (385.8 ± 353.8 minutes vs 855.9 ± 337.4 minutes; p < 0.0001). CONCLUSIONS: The results of this study have pointed to some important observations in this patient population. SA offers unique advantages in comparison with GA for performing MIS-TLIF, including reduced OR time and postoperative pain, and faster postoperative mobilization.