Completely switching from cigarette smoking to electronic nicotine delivery systems (ENDS) reduces exposure to toxic substances. Yet, many smokers believe that ENDS are at least as harmful as smoking, making them less likely to switch from cigarettes to ENDS. Effectively communicating reduced-exposure information is critical, but such messages must be properly understood. This online study evaluated comprehension of a factual message, indicating that smokers who switch completely away from smoking to JUUL-brand ENDS can reduce their exposure to harmful chemicals in cigarette smoke. Participants were 12 557 adults 18+ years (smokers, dual users and former and never users of tobacco) randomized to see the reduced-exposure message or to a Control condition. After exposure to the message, the majority of smokers (89%) understood the need to switch completely from cigarettes to JUUL to achieve reduced exposure. Most smokers and nonusers (>75%) did not misperceive JUUL as completely eliminating exposure to harmful chemicals, and >85% understood that using JUUL has risk. Exposure to the message improved understanding of the intended audience for JUUL. Individuals with limited health literacy showed modestly lower comprehension, regardless of condition. Ensuring adequate comprehension of messages about reduced exposure from ENDS is important to ensuring that such messaging can benefit public health.