Introduction: Cigarette smoking increases the risk of cardiovascular disease. Reduction in the levels of harmful constituents by heating rather than combusting tobacco without modifying the amount of delivered nicotine has the potential to reduce the risk of tobacco related disease. Aim: In this study, we investigated the effect of extract from a new candidate modified risk tobacco product (MRTP), the tobacco heating system (THS) 2.2, on the migratory behavior of monocytes in comparison with extract of smoke from combustible 3R4F reference cigarettes. Methods: The extracts were generated by aerosol-bubbling RPMI media from 3R4F and MRTP according to Health Canada standards. Endpoints included cytotoxicity (cell death assessed by 7-AAD staining followed by FACS analysis), inflammation (cytokine measurements), THP-1 cell migration (Boyden chambers), and transendothelial migration (TEM) determined by real-time impedance. Results: The results show that treatment of THP-1 cells with extract from 3R4F smoke or THS2.2 aerosol induced a concentration-dependent increase in cytotoxicity and inflammation (IL-8 and TNF-α secretion). The inhibitory effects of THS2.2 aerosol extract for chemotaxis and TEM were at least ~18 times less effective compared to 3R4F smoke extract. Furthermore, we found decreases in the integrity of a HCAEC monolayer in a concentration-dependent manner. However, for all other examined endpoints, the extract from 3R4F smoke showed more than one order of magnitude stronger effects than that from THS2.2 aerosol extract. Conclusion: These data indicate the potential of the Tobacco Heating System to reduce the risk for cardiovascular disease compared to combustible cigarettes.