To evaluate the efficacy and safety of the novel ultrasound-guided cervical sympathetic chain pulsed radiofrequency (PRF) for subacute herpes zoster neuralgia. Sixty patients with subacute herpes zoster neuralgia (one month until the third month after the rash onset) on the maxillofacial, head, and neck regions were enrolled in our study. Patients were randomized into two groups: sham-operated (sham) group (n = 30) and radiofrequency (RF) group (n = 30). In the RF group, the affected side cervical sympathetic chain was treated with bipolar high voltage long-duration PRF. In the sham group, the RF cannula was placed at the same position as in the RF group, but without RF energy application. The visual analog scale (VAS), Pittsburgh Sleep Quality Index (PSQI), 36-item Short Form Health Survey (SF-36), analgesic drug usage, incidence of postherpetic neuralgia, and adverse effects were recorded in both groups. In both groups, compared with preoperative, VAS and PSQI scores decreased, while SF-36 scores improved after the treatment (p < 0.05). The VAS and PSQI scores were significantly lower, whereas the SF-36 scores were significantly higher in the RF group than in the sham group at 1, 30, 90, and 180 days after the treatment (all p < 0.05), and the amount of analgesic drugs consumption was also lower in the RF group than in the sham group (p < 0.05). The incidence of postherpetic neuralgia was lower in the RF group than in the sham group (p < 0.05). No noticeable complications and side effects were observed in either group. The novel ultrasound-guided cervical sympathetic chain pulsed radiofrequency could effectively relieved subacute herpes zoster neuralgia (one month until the third month after the rash onset) on the maxillofacial, head, and neck regions, and reduced the incidence of postherpetic neuralgia.