The therapeutic effect of postherpetic neuralgia (PHN) is often disappointing and challenging. The role of intra-cutaneous injection of local anesthetic and steroids in preventing PHN remains unknown. The purpose of this study was to investigate the effect of a single intra-cutaneous injection of ropivacaine plus methylprednisolone on acute thoracic herpes zoster (HZ) pain intensity and duration, eruptive duration, and PHN incidence. A total of 97 patients with acute thoracic HZ diagnosed 1-7 days after the onset of the rash were randomly assigned to receive either 15 mL of 37.5 mg ropivacaine plus 40 mg methylprednisolone (active group, n = 49) or 15 mL of saline (placebo group, n = 48). Over 7 days, all patients received 800 mg of acyclovir 5 times daily and 150 mg pregabalin twice daily. Acetaminophen was used as a rescue analgesia when visual analog scale ≥4. Pain intensity was measured with visual analog scale and the amount of analgesic taken was evaluated at the initial visit and at weeks 1, 4, 12, and 24 after the intra-cutaneous injection. The time of complete resolution of pain, time of healing of skin eruption, and incidence of PHN were reported. The active group displayed a significantly shorter duration of pain (28.4 ± 46.7 vs. 59.2 ± 65.0, respectively;p= .009) and herpetic eruption (22.5 ± 6.8 vs. 32.6 ± 7.6, respectively;p< .001) than the placebo group. A significantly lower incidence of PHN was encountered in the active group after 4 weeks (16.3% vs. 47.9%, respectively;p= .001) and 12 weeks (10.2% vs. 29.2%, respectively;p= .019). Lower incidence of PHN was noticed in the active group after 24 weeks; however, this was not statistically significant (6.1% vs. 18.8%, respectively;p= .059). There was a significant reduction in the average and total doses of pregabalin and acetaminophen in the active group after the injection. No serious side effects were noticed during the study period. Early single intra-cutaneous injection, in combination with antiviral agents and optimal analgesics, in the course of acute thoracic HZ seems to be a simple, well-tolerated, and effective adjuvant treatment modality. It dramatically decreased pain intensity, shortened pain duration, reduced skin eruption, and reduced and may even prevent the development of PHN.