We provide one of the first formalizations of a vaccination campaign in a decision‐theoretic framework. We analyze a model where an ambiguity‐averse individual must decide how much effort to invest into prevention in the context of a rampant disease. We study how ambiguity aversion affects the effort and the estimation of the vaccine efficacy in clinical trials and immunization campaigns. We find that the behaviors of individuals participating in a clinical trial differ from individuals not participating. Individuals who are more optimistic toward vaccination participate more in trials. Their behaviors and efforts are also affected. As a result, because vaccine efficacy depends on unobserved behaviors and efforts, the biological effect of the vaccine becomes difficult to evaluate. During the scale‐up phase of a vaccination campaign, provided that vaccine efficacy is established, we show that vaccine hesitancy may still be rational.