OBJECTIVES: To examine the cost-effectiveness (CE) of brivudine over aciclovir in the treatment of herpes zoster in Germany. METHODS: This CE analysis used effectiveness data from a double-blind RCT comparing brivudine (125 mg p.o. once daily) with aciclovir (800 mg p.o. five times daily). Treatment with brivudine showed a 25% reduction in postherpetic neuralgia (PHN). Based on the IMS prescription index, the 2004 incidence of herpes zoster in Germany was 348,000 cases, with 15.74% consecutive cases of PHN under brivudine and 21% PHN cases under aciclovir. Cost data were obtained from public price lists. One therapy cycle with brivudine or aciclovir costs €95.67 and €32.83 respectively; analgesics for PHN cost an average €1500 annually. The study was conducted considering direct costs only. A sensitivity analysis accounted for varying costs for treating PHN and age-dependent PHN incidences. RESULTS: A total of 54,775 PHN cases under brivudine and 73,080 cases under aciclovir were calculated, producing total annual treatment costs of €115,455,660 and €121,044,840. Treatment with brivudine saved costs of €305.34 per PHN case avoided. The sensitivity analysis considered that 60% of herpes zoster patients are 60 years or older (IMS Disease Analyzer 2002), resulting in different numbers of PHN cases depending on age and antiviral therapy. ICERs of brivudine ranged for the older agegroup between €694.66 (PHN therapy cost: €500) and -€1805.34 (PHN therapy cost: €3000). Corresponding values for the younger agegroup were €1827.66 and -€672.34. Both antiviral therapies produced equal annual total therapy costs if PHN therapy amounted to €1200. CONCLUSIONS: Although three times more expensive, brivudine proved cost effective over aciclovir, producing savings if PHN therapy costs were equal to or higher than €1200. Since effective analgesic therapy would cost an average €3000 annually, brivudine may be recommended as first-choice treatment because of its cost-saving potential and convenient once-daily dosage.