Introduction Herpes zoster (HZ) is a disease caused by the reactivation of the varicella zoster virus. Postherpetic neuralgia (PHN) is the most common complication of HZ. Aim Repetitive paravertebral block with local anaesthetics and dexmedetomidine for the prevention of PHN in patients with acute herpes zoster. Material and methods 104 patients with acute herpes zoster were randomly divided into two groups. Group Rop received repetitive paravertebral block with 0.25% ropivacaine 20 ml per 72 h three times. Group Dex received repetitive paravertebral block with a mixture of 0.25% ropivacaine 20 ml and dexmedetomidine 20 µg per 72 h three times. Patients were permitted to take tramadol when the visual analogue scale (VAS) ≥ 4. The incidence of zoster-related pain was recorded at 1, 3, and 6 months after the end of treatments; VAS scores and the dose of rescue drug were recorded at 1 week, 2 weeks, 1 month, 3 months, and 6 months after the end of treatments. Results At 1 month post therapy, the incidence of zoster-related pain was 11% in Group Dex, compared with 35% in Group Rop ( p = 0.005). At 3 months post therapy, the incidence of zoster-related pain in Group Dex was still significantly lower than in Group Rop. The VAS scores and the dose of rescue drug in Group Dex were also significantly lower than in Group Rop at each time point ( p < 0.05). Conclusions Repetitive paravertebral block with local anaesthetics and dexmedetomidine in patients with acute herpes zoster can significantly reduce the incidence of zoster-related pain.