BACKGROUND: The safety and efficacy of transforaminal lumbar interbody fusion (TLIF) and posterior lumbar interbody fusion (PLIF) in lumbar spondylolisthesis have not been validated in many prospective randomized trials. AIM: We aimed to validate the safety and efficacy of TLIF and PLIF surgery in lumbar spondylolisthesis using the clinical, radiographic, and cost-utility outcomes. METHODS: The data of surgically treated single-level spondylolisthesis patients were randomized prospectively into two groups. The groups were compared regarding demographics, perioperative complications, hospital stay, total expenditure, fusion rate, and clinical outcomes (visual analog scale, Oswestry disability index, Zurich claudication scale, and Odom’s criteria). A review of literature was done to compare the outcomes with the ones from higher-income nations. RESULTS: Thirty-three patients underwent prospective randomization. The improvement in the clinical outcomes at 12-month follow-up showed improvement in the TLIF group more than the PLIF group but with no significant difference. The mean operative time was significantly longer in the PLIF (p < 0.05), also, the blood loss was significantly less in the TLIF (p < 0.001). The complications frequency did not show any statistical significance between both groups and no significant difference in the patient’s post-operative patient satisfaction (p = 0.6). The mean hospital stay was non-significantly longer in the PLIF (p = 0.7). At 12-month follow-up, 93.3% of the TLIF patients were fused versus 86.7% of the PLIF (p = 0.5). The total cost of the TLIF was significantly less (p < 0.001). CONCLUSION: Both PLIF and TLIF could achieve similar fusion rates and clinical satisfaction in the management of lumbar spondylolisthesis. The TLIF group was significantly better in terms of financial burden, operative time, and blood loss.