This study examines how optimistic bias moderates the association of direct-to-consumer prescription drug advertising (DTCA) exposure with consumers' responses to DTCA. We propose and test a model that addresses how exposure to DTCA plays a role in health risk assessment and prescription drug decision engagement. Findings from an online survey of U.S. adults (n = 628) demonstrated that exposure to DTCA is positively associated with consumers' perceived susceptibility and negatively associated with optimistic bias about health risk. The relationship between DTCA exposure and prescription decision engagement was mediated through perceived susceptibility, and this process was moderated by optimistic bias. The study's theoretical implications are discussed along with its consumer and public health implications.