Objective To investigate the early effectiveness of Zero-profile interbody fusion system (Zero-P) in the treatment of cervical disc protrusion. Methods Between October 2010 and June 2012, 25 patients with cervical disc protrusion underwent anterior cervical discectomy and fusion (ACDF) using the Zero-P system. There were 15 males and 10 females, aged from 35 to 68 years (mean, 49 years). The disease duration was 3-26 months (mean, 10.5 months). Single segment was involved in all cases (2 cases in C3, 4, 5 cases in C4, 5, 11 cases in C5, 6, and 7 cases in C6, 7). The operation time and blood loss were recorded and analyzed. The visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and neck disability index (NDI) were used to assess pain and nerve function improvement; the cervical Cobb angle was measured on the X-ray films before and after operation; according to Pitzen’s criteria, intervertebral fusion was evaluated. Results The operation was successful in 25 patients, with no severe complication. The average blood loss was 42.6 mL (range, 20-120 mL). The average operation time was 63.6 minutes (range, 45-90 minutes). Primary healing of incision was obtained in all cases; no injury of spinal cord and nerve root, cerebrospinal leakage, or deep infection occurred. The patients were followed up 6-23 months (mean, 14.5 months). No Cage subsidence and loosening, breaking, or pulling-out were observed. The symptoms and curvature of the cervical spine were obviously improved in all patients after operation. The VAS score, JOA score, NDI, and the cervical Cobb angle at 3 months and last follow-up showed significant differences when compared with preoperative ones (P lt; 0.05), but no significant difference was found between at 3 months and at last follow-up (P gt; 0.05). The interbody fusion was achieved in each operated segment of all patients according to Pitzen’s criteria. Conclusion The early effectiveness of ACDF with Zero-P system is satisfactory in treatment of cervical disc protrusion because it has the advantages of short operation time, less bleeding, good stability and restoration of the cervical alignment.