Background:Varicella zoster virus (VZV) exposure seriously threatens immunocompromised hosts. Postexposure prophylaxis (PEP) using immune globulins is considered the standard of care; however, the available literature is mainly based on its use in pediatric patients. Here, we describe a widespread VZV exposure among immunocompromised adults treated with VZV-specific immunoglobulins (VZVSIG), and we discuss management and outcomes.Methods:We conducted a retrospective study to describe the exposure of immunocompromised patients to a single healthcare worker with primary VZV in 2019. Patients were grouped by their overall risk for infection, and those at risk received a single intramuscular dose of 625 IU of VZVSIG and were followed for 1 year.Results:In total, 83 patients received PEP at <96 hours of exposure: 14 were hospitalized, 68 were outpatients, and 1 was an immunocompromised staff member. The median age was 69 years (range, 21–92), and 49.4% were male. In addition, 30% of the patients were deemed high risk, 42% were intermediate risk, and 28% were considered low risk, although they were given PEP. Varicella infection was not diagnosed in any patient in the first weeks of follow-up. However, during the year of follow-up, 4 patients developed symptoms suspicious of VZV, all >3 months after exposure, thus were probably unrelated to the event. Adverse events related to VZVSIG (pyrexia) were reported in 2 patients (2.4%).Conclusions:Our findings demonstrate the utility of VZVSIG as PEP in one of the largest cohorts of immunocompromised adults to date. No early varicella infection was found following exposure, supporting the current recommendations of the VZVSIG administration.