This comparative study explores incertitude about hepatitis B (HBV) and its implications for childhood vaccination in Bangui, Central African Republic, and the Cascades region, Burkina Faso. Anthropological approaches to vaccination, which counter stereotypes of “ignorant” publics needing education to accept vaccination, excavate alternative ways of knowing about illness and vaccination. We build on these approaches, evaluating different kinds of incertitude (ambiguity, uncertainty, ignorance) about infancy, HBV, health protection, and vaccination. Using interviews and participant observation, we find that Bangui and Cascades publics framed their incertitude differently through stories of infancy, illness, and protection. We locate different forms of incertitude within their historical contexts to illuminate why vaccination practices differ in the Cascades region and Bangui. A more nuanced approach to incomplete knowledge, situated in political, economic, and social histories of the state and vaccination, can contribute to more appropriate global health strategies to improve HBV prevention.