We compared the Tobacco Heating System (THS) 2.2 and conventional cigarettes (CCs). Biomarkers of exposure are reduced upon THS 2.2 use close to smoking abstinence. Subjects adapt quickly to THS 2.2 while maintaining their desired nicotine level. Reduction in urge-to-smoke was comparable between THS 2.2 and CCs. THS 2.2 was perceived as less rewarding than CCs.