E-cigarettes have recently become increasingly popular, especially amongst middle and high school students. Although they are marketed as safer alternatives to tobacco cigarettes, they produce toxic metals and carcinogenic nitrosamines. This thesis studies the effects of e-cigarette aerosol on the growth and proliferation of oral epithelial cells because the consequences of vaping, including a potential risk for aberrant growth leading to cancer, are not well understood. Cells were grown in matrigel, causing the formation of three-dimensional spheroids modeling the physiological architecture of the oral epithelium. Those spheroids were chronically exposed to vape with different treatment conditions to study the functional biological effects of the presence of nicotine, dosage, and different types of exposure. The diameter of the spheroids was measured throughout the process as an indicator of cell growth. It showed that the vape exposure, especially nicotine-rich aerosol, induces an increase in spheroid diameter in a dose-dependent manner. The increased cell growth is supported by enhanced metabolic activity as well as increased aldehyde dehydrogenase activity, a marker of stemness prominently upregulated in cancer stem cells. Protein was extracted at the end for protein expression analysis through Western blotting and the identification of the activation of survival signaling pathways and stem cell markers. Lastly, spheroids were co-cultured with Strep. mutans, a cariogenic bacterial resident in the oral cavity, and acutely exposed to vape. Co-culture with S. mutans did not significantly affect spheroid growth under the current experimental conditions or significantly change the expression patterns of proliferation and tumor initiation proteins. Future research will include tumorigenic assays and investigate how vape may induce carcinogenesis of the oral epithelium.