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The aim of this study is to assess the long-term outcomes after performing the four-level anterior cervical discectomy and fusion (ACDF) in the treatment of degenerative cervical spine disease using stand-alone titanium cages. Overview of Literature: Over the last decades, a rapid increase in the use of stand-alone cages for ACDF has been observed. However, research on their application in the treatment of four-level diseases is insufficient. Methods: In this study, 130 patients presenting with symptomatic cervical spondylosis who underwent four-level ACDF using standalone cages in our institution between 2008 and 2016 were assessed. Fifty-two patients were women and 78 men with a mean age of 60.5 years. Their clinical and radiological outcomes were assessed. The results of the Neck Disability Index (NDI) and Visual Analog Scale as well as bony fusion were evaluated, and the revisions were analyzed. All of the patients underwent the four-level microscopic ACDF using the same titanium rectangular cage. Results: The mean follow-up was 47±11.4 months. A fusion of all four levels was achieved in 80.72% of the patients. In 25 patients (19.23%), an incomplete bony bridging was observed in at least one fusion level at the final follow-up. However, only two patients (1.5%) were symptomatic and underwent revision. The mean NDI improved significantly from 39.4±9.3 at presentation to 8.3±6.6 at the final follow-up. Cervical lordosis improved significantly from a mean of 5.5° preoperatively to a mean of 15° postoperatively. Cage sinking and loss of segment height during healing had a mean of 3 mm. Conclusions: Overall, the application of four-level ACDF using titanium cages in a stand-alone technique has been proven to be a safe and effective treatment method for degenerative disease. In a large cohort, a high rate of good long-term clinical and radiological results was achieved.