Background: This was a pre-market actual use study with the Tobacco Heating System (THS), a candidate modified risk tobacco product, conducted with adult smokers in eight cities in the United States. The main goal of the study was to describe THS adoption in a real-world setting. The aim of this analysis was to identify potential predictors for adoption of THS using stepwise logistic regression method. Methods: This actual use study was an observational study assessing self-reported stick-by-stick consumption of the THS product compared with the use of commercial cigarettes over six weeks. The study aimed at replicating the usage of THS in real-world conditions with participants being able to consume cigarettes, THS, and any other nicotine-containing products (e.g., e-cigarettes, cigars, etc.) ad libitum. Results: 14.6% of participants adopted THS, which comprised 70% or more of their total tobacco consumption by the end of the observational period (in Week 6). The main predictors of adoption were the liking of the smell, taste, aftertaste, and ease of use of THS. The proportion of adoption was higher in participants aged 44 years and older and in Hispanic or Latino adult smokers. Additionally, adoption of THS was more likely in participants who had never attempted to quit smoking and in participants who smoked up to 10 cigarettes per day. Finally, the adoption of THS was higher in participants who consumed both regular and menthol THS compared with those who consumed only one THS variant. Conclusions: The main predictors of THS adoption were positive sensory assessment and the ease of use. Socio-demographic characteristics and smoking habits appeared much less important. Post-marketing studies will provide further insights on the impact of the THS at the individual and the overall population level.