PROJECT SUMMARY Nearly 70% of the ~ 30 million adult cigarette smokers in the US want to quit, and 55% report trying to quit at least once in the past year - yet, over 90% fail despite using smoking cessation medication. The average smoker will attempt to quit smoking at least 30 times before abstaining for 12 months or longer. These attempts typically occur over decades of smoking, carcinogen and toxicant exposure, resulting in 480,000 deaths annually. Novel alternatives must be considered to significantly reduce the combustible cigarette-attributable morbidity and mortality among smokers unable to quit with traditional approaches. The Surgeon General’s Report and others have underscored that helping smokers who cannot quit smoking switch to less harmful nicotine-containing products – a harm reduction approach - can dramatically reduce this health burden. E-cigarettes (ECIGS), and oral nicotine pouches (ONPs), expose users to few of the chemicals found in cigarette smoke and are thus promising noncombustible harm reduction tools for smokers who would not otherwise quit smoking. For their harm reduction potential to be realized, fundamental questions must be answered. One, can persistent smokers switch from combustible cigarettes to either ECIGS or ONPS? Initial research suggests that one- third of smokers fully switch to ECIGS, although comparable data is unavailable for ONPS. Two, what factors influence switching? The factors affecting the transition to ECIGS or ONPS have yet to be investigated. Three, does one of these noncombustible alternatives expose users to lower levels of harmful chemicals than the other? Only limited, indirect, and industry-sponsored data exist. Documenting the relative success of switching to ECIGS or ONPS, identifying drivers of switching, and quantifying the associated harm reduction will inform research to optimize smokers’ success in transitioning from combustible cigarettes. We propose the first longitudinal investigation of the subs