This study is part of the clinical program to assess Tobacco Heating System 2.2 (THS 2.2), a candidate modified risk tobacco product. The objective was to demonstrate reduction in exposure to selected harmful and potentially harmful constituents after 5 days of use of THS 2.2 compared to combustible cigarettes (CC). Puffing topography (PT) and product evaluation were recorded.This was an open-label, randomized, controlled, 3-arm parallel group, confinement study in 160 healthy smokers. Subjects used their preferred brand of CC at baseline, and were subsequently randomized to continuing to smoke CC, to switch to THS 2.2 or to stop smoking for 5 days. This was an ad-libitum product use study. PT is the description of puff characteristics (e.g. puff volume, duration or interval) and was assessed using a Smoking Puff Analyzer Mobile (SODIM®) with pressure and flow measurement capabilities. PT parameters were recorded at baseline for all subjects, and at Day 1 and Day 4 for both the CC and THS 2.2 arms. Product evaluation was assessed daily using the Modified Cigarette Evaluation Questionnaire (mCEQ). 24-hour urine was collected to evaluate the levels of biomarkers of exposure, reported in another abstract. This study was conducted according to GCP and is registered with ClinicalTrials.gov, number NCT01959932. There were no notable differences in puff volume, number of puffs and total volume of puffs between the THS 2.2 and the CC arms. The puff duration increased in the THS 2.2 arm from 1.50 s at baseline to 1.91 s on Day 4. Puff duration did not change CC arm.No notable difference was seen between the THS 2.2 and CC arm on Day 5 in any of the mCEQ subscales. The average daily product use between baseline and the end of exposure slightly increased in the THS 2.2 arm (from 16 CC to 20.7 THS sticks), and remained in the same range in the CC arm (from 16.2 CC to 16.6 CC). The Nicotine Equivalents were similar in both arms throughout the exposure period. In conclusion, a comparable puffing topography and product use pattern was observed, which together with no notable difference in mCEQ and comparable levels of nicotine uptake indicated an easy adaptation to THS 2.2.