Transforaminal lumbar interbody fusion (TLIF) and dual-approach anteroposterior (AP) are common techniques to achieve circumferential fusion for lumbar spondylolisthesis. It is unclear which approach is more cost-effective. Our goal was to determine the incremental cost-effectiveness ratio (ICER) by calculating the cost per quality-adjusted life year (QALY) for each approach. This study is a propensity-matched cost-effectiveness comparison. Patients with lumbar spondylolisthesis undergoing single-level AP fusion or TLIF and enrolled in a prospective observational surgical database were included in this study. The outcome measures in this study were the Oswestry Disability Index (ODI) and the Short Form-6D (SF-6D). From a prospective surgical database, patients with lumbar spondylolisthesis undergoing single-level AP fusion were propensity matched to a TLIF cohort based on age, gender, body mass index, smoking status, workers compensation, preoperative ODI, and back and leg pain numeric scores. Quality-adjusted life years gained were determined using baseline and 1- and 2-yearpostoperative SF-6D scores. Cost was calculated from actual, direct hospital costs and included subsequent postsurgical costs (epidural spinal injections, spine-related emergency department visits, readmissions, and revision surgery). Thirty-one cases of AP fusions were identified and propensity matched to 31 TLIF patients. Patients undergoing TLIF had a shorter mean operative time (270 vs. 328 minutes, p=.039) but no difference in estimated blood loss (526 vs. 548 cc, p=.804) or hospital length of stay (4.5 vs. 6.1 days, p=.146). Quality-adjusted life years gained at 2 years were also similar (0.140 vs. 0.130, p=.672). The mean index surgery and the total 2-year costs were lower for TLIF compared with AP (index: $29,428 vs. $31,466; final: $30,684 vs. $331,880). As overall costs were lower and QALYs gained were similar for TLIF compared with AP fusion, TLIF was the dominant intervention with an ICER of $116,327. Under our study parameters, surgical treatment of lumbar spondylolisthesis with TLIF is more cost-effective compared with AP fusion. Because of the short-term follow-up, the longevity of this should be further investigated.