Objective. This qualitative study of a select sample of vaccine-hesitant parents (VHPs) explores perceived and constructed personal judgments about the risks and uncertainties associated with vaccines and vaccine-preventable diseases (VPDs) and how these subjective risk judgments influence parents’ decisions about childhood vaccination. Methods. The study employed semistructured focus group interviews with 42 VHPs to elicit parents’ perceptions and thought processes regarding the risks associated with vaccination and nonvaccination, the sources of these perceptions, and their approach to decision making about vaccination for their children. Results. VHPs engage in various reasoning processes and tend to perceive risks of vaccination as greater than the risks of VPDs. At the same time, VHPs engage in other reasoning processes that lead them to perceive ambiguity in information about the harms of vaccination—citing concerns about the missing, conflicting, changing, or otherwise unreliable nature of information. Conclusions. VHPs’ refusal of vaccination may reflect their aversion to both the risk and ambiguity they perceive to be associated with vaccination. Mitigating this vaccine hesitancy likely requires reconstructing the risks and ambiguities associated with vaccination—a challenging task that requires providing parents with meaningful evidence-based information on the known risks of vaccination versus VPDs and explicitly acknowledging the risks that remain truly unknown.