BACKGROUND: Non-contiguous two-level Anterior Cervical Discectomy and Fusion (ACDF) may be a viable option for patients with degenerative cervical myelopathy and imaging-evident spine and radicular compression at two non-contiguous cervical levels. The risk of hastening degeneration and triggering Adjacent Segment Disease at the spine levels located between the fused levels is a putative adverse event, which was assessed in a few studies. The aim of this study is to investigate the clinical outcomes of patients undergoing non-contiguous two levels ACDF and to assess biomechanical modifications at non-fused segments. METHOD: We retrospectively reviewed all patients with noncontiguous two-level spine and radicular compression, who underwent simultaneous noncontiguous two-level ACDF at our center. We analyzed clinical and radiological outcomes and investigated the rate of adjacent segment disease. Radiographic parameters were calculated on pre- and postoperative images. RESULTS: Thirty-two patients underwent simultaneous noncontiguous two-level ACDF for cervical myelo-radiculopathy between 2015 and 2021 and were followed up for a mean period of 43.3 months. For all patients, the mJOA score significantly improved from 14.57 ± 2.3 to 16.5 ± 2.1 (p<0.01) and the NDI score significantly decreased from 21.45 ± 4.3 to 12.8 ± 2.3 (p<0.01) postoperatively. Cervical lordosis increased after surgery (from 9.65° ±9.47 to 15.12° ± 6.09); intermediate disc height decreased (5.68 mm ± 0.57 to 5.27 mm ±0.98); the ROMs of intermediate (from 12.45 ± 2.33 to 14.77 ± 1.98), cranial (from 14.63 ± 1.59 to 15.71 ± 1.02), and caudal (from 11.58 ± 2.32 to 13.33 ± 2.67) segments slightly increased. During follow-up assessment, in one patient the myelopathy worsened due to spine compression at the intermediate level. CONCLUSIONS: Simultaneous and non-contiguous two-level ACDF is a safe and effective procedure. The occurrence of postoperative adjacent and intermediate segment disease is rare.