Adults who smoke (AWS) who switch completely to e-cigarettes reduce their exposures to many harmful chemicals in cigarette smoke. Those who believe e-cigarettes are less harmful than cigarettes are more likely to use e-cigarettes to switch away from smoking, yet most believe e-cigarettes are at least as harmful as cigarettes. This study assessed the effect on risk perceptions of communicating that switching can reduce exposure to harmful chemicals from cigarette smoke. In a randomized experiment, AWS (n = 3485), dual users (DU) of cigarettes and e-cigarettes (n = 1756), and nonusers (n = 7316) viewed an ad for JUUL with or without a reduced-exposure message, and completed assessments of perceived risk. Message exposure decreased perceived risk of JUUL among adults who smoke, while increasing perceived risk of smoking, thus increasing the perceived risk differential (PRD). Among DU, the message increased perceived risk of smoking, but did not change perceived risk of JUUL. Among nonusers, who rated the perceived risk of all assessed tobacco products higher than did AWS and DU, the message decreased perceived risk of JUUL, and did not affect perceived risk of smoking. Accurate modified exposure communications have potential public health benefit by shifting the PRD of smoking and e-cigarettes.