Varicella can be severe in adults. When universal vaccination is not adopted, post-exposure prophylaxis has been recommended in adults with uncertain history of varicella to reduce the burden of the disease in adults, however its impact is not quantified.We developed a Bayesian probabilistic framework to estimate the impact of post-exposure prophylaxis in adults. We hypothesized that post-exposure vaccination would be proposed only after varicella exposure in close relatives. Information regarding the nature of the culprit exposure was obtained from a sample of 221 adult varicella cases. The lifelong probability that adults aged 18 would be infected with varicella was determined using data from the French Sentinelles surveillance network. Estimates of post-exposure vaccination efficacy were then used to compute the number of cases and hospitalizations prevented in adults. Familial exposure to varicella was reported by 81 adult cases out of 221. The probability of infection after exposure was 32%, so that 6 exposures on average were necessary to explain the observed cumulated lifetime incidence of varicella in non-immune 18 years old and over adults. Among the 35% of the 18 years old population with uncertain history of varicella, 11% would truly be non-immune. Post-exposure vaccination would prevent 26% of the cases (13 cases prevented per 100,000 adults per year) and 31% of the hospitalizations (0.2 hospitalizations prevented per 100,000 adults per year) if vaccination acceptance was 70%. An average of 16 adults would be vaccinated to avert one varicella case.Post-exposure vaccination is associated with a substantial decrease in the burden of the disease in adults in a country where universal vaccination is not recommended. This quantitative information may help inform professionals to uphold the recommendation.