The study compared clinical characteristics and caries risk assessments between tobacco heating system (THS) smokers, cigarette smokers and non-smokers. General data, data regarding fluoridation, smoking and dietary habits was obtained through a questionnaire. Caries experience was assessed by the DMFT index; the amount of biofilm by the Full mouth plaque score index; the amount of salivation by the quantum of stimulated salivation test; salivary pH with pH indicator strips and salivary number of S.mutans and Lactobacilli by cultivation on agar plates. The Cariogram method was used to assess caries risk. No differences between the groups was detected regarding education level, average daily number of meals, fluoridation programs, systemic diseases, and caries experience. The groups significantly differed in the amount of salivary S.mutans and Lactobacilli (p < 0.001), accumulated biofilm (p = 0.034), salivation quantum (p < 0.001), and saliva pH (p = 0.009). Exposure to tobacco smoke and heated tobacco aerosol increased the accumulation of biofilm and decreased salivary pH. Smoking increased S. mutans, while THS consumption decreased salivation and Lactobacilli the most. The Cariogram analysis found no differences in chances of avoiding new caries lesions between the groups, but a significant difference in developing caries lesions due to dietary habits was detected (p < 0.001) with non-smokers having higher risk than smokers, but not than THS consumers. THS and cigarette smoking were related to clinical characteristics that affect caries activity even though the caries risk assessment revealed no significant difference in the chances of avoiding new caries lesions between the groups. THS and cigarette smokers could have higher caries activity than non-smokers. The clinical study protocol has been registered on ClinicalTrials.gov under the ID number: NCT06314100.