Prospective cohort study. To perform a cost-utility analysis and to investigate the clinical outcomes and patient's quality of life after anterior cervical discectomy and fusion (ACDF) to treat cervical spondylosis compared between fusion with polyetheretherketone (PEEK) and fusion with tricortical iliac bone graft (IBG) in Thailand. ACDF is one of the standard treatments for cervical spondylosis. The fusion material options include PEEK and tricortical IBG. No previous studies have compared the cost-utility between these 2 fusion material options. Patients with cervical spondylosis who were scheduled for ACDF at Siriraj Hospital (Bangkok, Thailand) during 2019-2020 were prospectively enrolled. Patients were allocated to the PEEK or IBG fusion material group according to the patient's choice of fusion material. EuroQol-5 dimensions 5 levels and relevant costs were collected during the operative and postoperative periods. A cost-utility analysis was performed using a societal perspective. All costs were converted to 2020 United States dollars (USD), and a 3% discount rate was used. The outcome was expressed as the incremental cost-effectiveness ratio. Thirty-six patients (18 ACDF-PEEK and 18 ACDF-IBG) were enrolled. Except for Nurick grading, there was no significant difference in patient baseline characteristics between groups. The average utility at 1 year after ACDF-PEEK and ACDF-IBG were 0.939 ± 0.061 and 0.798 ± 0.081, respectively ( P < 0.001). The total lifetime cost of ACDF-PEEK and ACDF-IBG was 83,572 USD and 73,329 USD, respectively. The incremental cost-effectiveness ratio of ACDF-PEEK when compared with that of ACDF-IBG showed a gain of 4468.52 USD/quality-adjusted life-years, which is considered cost-effective at the Thailand willingness-to-pay threshold of 5115 USD/quality-adjusted life-year gained. ACDF-PEEK was found to be more cost-effective than ACDF-IBG for treating cervical spondylosis in Thailand. Level II.