Abstract Background Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. Objectives To assess whether COVID-19 vaccine is associated with Varicella zoster virus induced neurologic disease (VZV-ND). Methods This was a multicenter retrospective case-control study with a test-negative design conducted at twelve hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021, and matched controls with a negative PCR VZV in CSF. Result We identified 188 patients meeting the case definition of VZV-ND admitted during the study period. Case patients were matched with 376 controls. There was no significant variation in the incidence of VZV-ND cases between one year period preceding and one year period following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least one dose of COVID-19 vaccine (N= 259) showed similar proportions of VZV-ND and non-VZV-ND in four time intervals (30, 42, 50, 60 days) following the last vaccine dose. Median time from the last vaccine dose to hospitalization with neurological syndrome, was 53 days (IQR 25-128) and 82 days (IQR 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (p=0.056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% versus 35.4%, p=0.2). Conclusion We did not find an association between COVID19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommends yearly, every fall and winter, establishing the safety of the vaccine is of great importance.