Background and Objectives: This study aimed to evaluate the clinical effectiveness and safety of ultrasound-guided pharmacopuncture (UGP) in comparison to non-guided pharmacopuncture (NGP) for the treatment of acute cervical myofascial pain syndrome (C-MPS) in primary care settings. Materials and Methods: This multi-center, prospective observational study included 97 patients diagnosed with acute C-MPS. Participants received a single session of either UGP or NGP at one of seven primary care institutions. Pain intensity was measured using the Numerical Rating Scale (NRS), and cervical function was assessed through active Range of Motion (ROM) tests conducted before and after treatment. We conducted follow-up interviews within 48 h after treatment to monitor adverse events. Results: Both groups showed significant improvements in pain levels and cervical ROM after treatment. The UGP group showed a greater reduction in NRS scores compared to the NGP group (p < 0.001). Notable enhancements in cervical extension and rotation on the affected side were also observed in the UGP group (p < 0.01), whereas changes in flexion and lateral flexion were similar between the two groups. No serious adverse events were reported. Conclusions: UGP has shown superior pain reduction and a greater improvement in specific cervical motions compared to non-guided treatments, indicating enhanced precision and therapeutic efficacy. Furthermore, no serious adverse events were reported, suggesting that UGP is a safe and effective non-surgical intervention for acute C-MPS in real-world primary care settings.