BACKGROUND Neck pain is a prevalent and burdensome health issue, with autologous conditioned serum (ACS), like Orthokine, being a recognized treatment for musculoskeletal conditions due to its anti-inflammatory effects. However, the optimal ACS administration method for neck pain remains unclear. The existing literature lacks robust evidence, especially for different injection techniques. This study aimed to compare ACS infiltration into cervical fascia with periarticular administration to determine if the former is as effective in alleviating neck pain, offering a novel approach to its management. MATERIAL AND METHODS Our study is designed to be a single-center, prospective, randomized trial involving 100 patients. Group A (n=50) will receive ACS through fascial infiltration at tender points under ultrasound guidance, with 4 doses administered every 3 days. Group B (n=50) will receive ACS injections in the articular column (facet joints) using the same dosing schedule. We will collect data at T0 (before therapy), T1 (6 weeks after therapy), and T2 (12 weeks after therapy), assessing outcomes with the Numerical Pain Scale (NRS), Neck Disability Index (NDI), and Dynamic Proprioception Test (DPT). RESULTS Enrollment begins in August 2023, and the study is set to conclude in July 2024. If data analysis, manuscript preparation, and peer review proceed smoothly, we anticipate publishing the results in late 2024 or early 2025. CONCLUSIONS If fascial infiltration with ACS proves equally effective as the standard periarticular method, it offers promise for patients on long-term anticoagulant treatment. Paravertebral injections in such cases carry a significant risk of bleeding, making ACS infiltration a potentially safer alternative for managing neck pain in these individuals.