The Glas G² ENDS is a temperature-regulated nicotine salt pre-filled disposable pod connected system with two power settings designed to minimize the combustion byproducts across a range of operating environments. Comparatively, the combustible cigarettes can reach temperatures of 1000 degrees Celsius and consequently generate over seven thousand thermal degradation products including compounds characterized as Harmful and Potentially Harmful Constituents (HPHCs). Seven different e-liquids (three tobacco, two menthol, two fruit; 50 mg/ml nicotine) were analyzed for HPHCs and compared to a 3R4F Kentucky Reference Cigarette and a market tobacco cigarette, Marlboro Gold. The Glas e-liquids were vaped under both nonintense and intense puffing conditions and combustible tobacco cigarette were smoked under intense puffing regime. No significant increase in the HPHC profile was observed with the two power settings, vaped under non-intensive and intense conditions, therefore presenting minimal risk to the consumers. On a per day use basis (e-liquid consumption for Glas e-liquids and cigarette use for tobacco products), there was a significant reduction in nicotine minor alkaloids (98%), carbonyl compounds (95-99%), volatile organic compounds (VOCs) (99%), metals (45-95%). On a product use per mg nicotine basis, carbonyl compounds, nicotine alkaloids, VOCs, and metals (cadmium and lead) levels were 95% to 99% lower and nickel was about 25%-60% lower than 3R4F and Marlboro Gold. This comparative HPHC analysis demonstrated that Glas test products in combination testing with the Glas G² device with two power settings yielded significantly lower HPHC compared to combustible tobacco cigarettes.