OBJECTIVES: Herpes zoster ophthalmicus (HZO) occurs when the varicella-zoster virus is reactivated in the ophthalmic division of the trigeminal nerve, either with or without ocular involvement. Serious sequelae, including chronic ocular inflammation, vision loss, and disabling pain can occur in patients with ocular involvement. Our previous study reported that herpes zoster (HZ) vaccine was effective in protecting against HZO with ocular involvement. The aim was to confirm this observation by taking advantage of a novel natural language processing (NLP) algorithm to identify HZO patients with ocular involvement avoiding time-consuming chart review METHODS: This study included Kaiser Permanente Southern California members who were at least 60 years old. The vaccinated cohort included 176,078 members who received HZ vaccine during 01/01/2007 through 12/31/2014. Each vaccinated member was matched to three unvaccinated members on age, sex, and length of membership. Individuals were passively followed through their electronic health records to identify incident HZ cases, who were further classified into HZO with ocular involvement, HZO without ocular involvement, and other HZ using a validated NLP algorithm applied to free-text clinical records. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) associated with vaccination.  RESULTS: The number of HZO cases with ocular involvement was 293 in 653,734 person-years (0.4 per 1,000 person-years; 95% CI, 0.4-0.5) among the vaccinated and 1,258 in 1,400,716 person-years (0.9 per 1,000 person-years; 95% CI, 0.8-0.9) among the unvaccinated. HZ vaccination was associated with a reduced risk of HZO with ocular involvement (adjusted HR=0.41; 95% CI, 0.35-0.48). The reduced risk was more prominent compared to HZO without ocular involvement (adjusted HR=0.65; 95% CI, 0.58-0.73) and other HZ (adjusted HR=0.50; 95% CI, 0.48-0.52).  CONCLUSIONS: This large scale study confirms our previous observation that HZ vaccine provides better protection against HZO with ocular involvement than against other HZ or against HZO without ocular involvement.