: Degenerative lumbar spine disease (DLSD) is increasingly managed with minimally invasive surgery (MIS) and evolving anesthesia methods. While general anesthesia (GA) remains standard, spinal anesthesia (SA) may offer faster recovery and fewer side effects. This study compares the clinical and economic outcomes of GA versus SA in transforaminal lumbar interbody fusion (TLIF). : A retrospective review of 18 TLIF patients (2018-2022) was performed, with 9 patients in each cohort. Patients were matched by demographics and procedure type. Data collected included operative time, blood loss, complications, postoperative opioid utilization, and 30-day readmissions. Costs were analyzed in categories: anesthesia, implants, inpatient care, operating room (OR) supplies, OR time, and PACU fees, using Wilcoxon Rank T-tests and Pearson Chi-Squared tests. : Clinical outcomes such as blood loss, and operative time were similar between groups. However, SA patients had significantly shorter LOS compared to GA (SA: 12 h vs. GA: 84 h, % difference: -150%, = 0.04). Additionally, SA patients had lower total direct costs ($27,881.85 vs. $35,669.01; = 0.027). Significant cost reductions with SA were noted in OR supplies/medications ($7367.93 vs. $10,879.46; = 0.039) and inpatient costs ($621.65 vs. $3092.66; = 0.027). Within these categories, reductions were observed for intravenous solutions, sedatives/anesthetics, pressure management, labs, imaging, evaluations, hospital care, and medications. Although costs for implants, anesthesia care, OR time, and PACU fees were lower with SA, these differences did not reach statistical significance. : In TLIF for DLSD, SA provides significant economic advantages over GA while yielding comparable clinical outcomes. These results support SA as a cost-effective alternative, warranting further prospective studies to confirm these findings.