In vitro toxicological methods are used to assess the biological activities of combustible and next generation tobacco products (NGP), including Heated Tobacco Products (HTP). To determine the genotoxic potential of aerosols generated from four HTP (glo™) styles, a marketed HTP comparator and three combustible cigarettes (CC), the bacterial reverse mutation (Ames) and in vitro micronucleus (IVMN) assays were conducted using test sample preparations of total particulate matter (TPM) combined with gas vapor phase (GVP). Equal volumes of the TPM and GVP fractions were combined (HC T-502) to represent “whole aerosol/smoke” from each product and used for Ames and IVMN exposures. Ames preincubation assays utilized tester strains TA98, TA100, TA1535, TA1537 and TA102 (±S9; HC T-501/OECD 471). For the IVMN assay, CHO cells were exposed under four schedules (3 Hr±S9 and 24 Hr-S9 with and without 24 h recovery; HC T-503/OECD 487, Thorne et al, 2019). In the Ames assay, all CC were mutagenic based on positive responses in 3 of 5 test strains, while the HTP were negative across all strains and test conditions (±S9) when tested at nicotine equivalent doses up to 10-fold greater than CC. In the IVMN assay, all CC produced positive genotoxic responses under all exposure schedules as indicated by dose-related increases in micronuclei. In contrast, genotoxic responses of only some HTP demonstrated positive genotoxicity under certain treatment. Additionally, nicotine-equivalent doses required for positive HTP genotoxicity ranged from 7.5-10x that of the CC.These results add to the weight of evidence from multiple studies showing that HTPsare less genotoxic/potentially harmful compared to CCs and align with the establishedtobacco harm reduction paradigm of NGPs.