Exposure to HPHCs following a complete or partial switch from combustible cigarettes was evaluated in an 8-week, randomized, open-label, parallel-cohort study. Healthy adult smokers who were not current ENDS users and who were not otherwise intending to stop smoking were enrolled. All subjects smoked their own-brand cigarettes through baseline and were randomized to receive a RELX Infinity ENDS with a prototype tobacco (Cohort A) or menthol flavored (Cohort B) e-liquid based on their own-brand combustible cigarette flavor, both RELX Infinity prototype flavored e-liquids (Cohort C), or to continue smoking (Cohort D). Subjects returned to the clinic every 2 weeks to complete study assessments. Subjects who completely or partially switched were categorized based on self-reported cigarette use, exhaled carbon monoxide (ECO), and urinary NNAL. A total of 194 subjects were randomized and 170 subjects completed the study. At 8 weeks, ~30% of subjects in the Infinity cohorts were deemed to have completely switched from cigarettes. Levels of nine non-nicotine urinary HPHCs were reduced by ~40-95% compared with baseline in subjects who completely switched to Infinity products while ECO was ~90% lower. In an exploratory summary of subjects who partially switched, the urinary HPHCs were reduced by ~15-35% compared with baseline while ECO was ~65% lower. Urine nicotine equivalents were unchanged in the subjects who partially switched while increases were observed in those who completely switched. Increases in urinary propylene glycol were also noted to varying extents in all analysis populations. These results suggest that smokers who partially or completely replace cigarettes with the RELX Infinity ENDS may experience reduced exposure to HPHCs found in cigarette smoke.