| Summary: | <i>Introduction</i>: Research from Philip Morris International’s science division on its Heat-not-Burn product IQOS<sup>TM</sup> focused on its chemical, toxicological, clinical, and behavioral aspects. Independent research on the experiences and behavioral aspects of using IQOS<sup>TM</sup>, and how it compares to e-cigarettes, is largely lacking. The current randomized, cross-over behavioral trial tried to bridge the latter gaps. <i>Methods</i>: Participants (<i>n</i> = 30) came to the lab on three consecutive days after being overnight smoking abstinent. During each session, participants used one of three products (cigarette, e-cigarette, or IQOS<sup>TM</sup>) for five minutes. Exhaled CO (eCO) measurements and questionnaires were repeatedly administered throughout the session. <i>Results</i>: Smoking a cigarette for five minutes resulted in a significant increase of eCO, whereas using an IQOS<sup>TM</sup> resulted in a small but reliable increase (0.3 ppm). Vaping did not affect eCO. Cigarette craving reduced significantly after product use, with the decline being stronger for smoking than for e-cigarettes or IQOS<sup>TM</sup>. Withdrawal symptoms declined immediately after smoking or using IQOS<sup>TM</sup>, and with some delay after vaping. IQOS<sup>TM</sup> scored higher in terms of subjective reward/satisfaction and was slightly preferred to the e-cigarette. <i>Discussion</i>: Short-term use of IQOS<sup>TM</sup> has a minimal impact on eCO, is equally effective in reducing cigarette craving and withdrawal symptoms as an e-cigarette, and is slightly preferred.
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