Increasing audience knowledge is often set as a primary objective of risk communication efforts. But is it worthwhile focusing risk communication strategies solely on enhancing specific knowledge? The main research questions tackled in this paper were: (1) if prior audience knowledge related to specific radiation risks is influential for the perception of these risks and the acceptance of communicated messages and (2) if gender, attitudes, risk perception of other radiation risks, confidence in authorities, and living in the vicinity of nuclear/radiological installations may also play an important role in this matter. The goal of this study was to test empirically the mentioned predictors in two independent case studies in different countries. The first case study was an information campaign for iodine pre-distribution in Belgium (N = 1035). The second was the information campaign on long-term radioactive waste disposal in Slovenia (N = 1,200). In both cases, recurrent and intensive communication campaigns were carried out by the authorities aiming, among other things, at increasing specific audience knowledge. Results show that higher prior audience knowledge leads to more willingness to accept communicated messages, but it does not affect people’s perception of the specific risk communicated. In addition, the influence of prior audience knowledge on the acceptance of communicated messages is shown to be no stronger than that of general radiation risk perception. The results in both case studies suggest that effective risk communication has to focus not only on knowledge but also on other more heuristic predictors, such as risk perception or attitudes toward communicated risks.