Introduction:The economic burden of herpes zoster (HZ), including its most common complication, postherpetic neuralgia (PHN), and its impact on health-related quality of life (HRQL) is not well described in Spain. The aim of this study was to estimate HZ-related healthcare costs and impact on HRQL in Spanish adults aged 50 years or older. Methods: A prospective, observational study was performed with patients with HZ recruited through four general practitioner networks in Spain (NCT01521286). HRQL data were collected using the EuroQoL-5 Dimension (EQ-5D) questionnaire; HZ-related pain and associated interference with activities of daily living (ADL) were assessed using the Zoster Brief Pain Inventory (ZBPI) questionnaire at days 0 (HZ rash onset), 15, 30, 60, and 90; patients with PHN were assessed up until day 270. Medical resource utilization was recorded throughout study follow-up. Work loss for patients/caregivers was also assessed. Costs were calculated from both the payer and societal perspectives. Results: A total of 545 patients with Hz were included, of whom 25 developed PHN. During days 0-30 post HZ diagnosis, the mean EQ-5D utility score was 0.738, equating to a utility loss of 0.138. Sleep was the ADL most affected component. The mean costs for HZ in the overall cohort were €240 and €296 from the payer/societal perspective, respectively; €187/ €242 for patients with HZ without any HZ-related complications; and €571/€712 for patients who developed PHN. The majority of costs were incurred during days 0-30. Conclusions: In Spain, HZ and HZ-related complications such as PHN reduce patient HRQL and increase the economic burden for both payers and society in general. Trail Registration: ClinicalTrials.gov identifier NCT01521286.