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Background: The cigarette smoking and its effect on the inflammatory cytokine levels in the smoker's saliva depicted the influence of electronic cigarettes on oral cytokine levels in oral fluids are scarce in the literature. Objectives: The present trial was conducted to compare and determine the proinflammatory and anti-inflammatory cytokines in whole stimulated saliva samples of electronic cigarette smokers, conventional smokers, and participants with no smoke exposure. Materials and Methods: Sixty adult participants were divided into the following four groups of nonsmokers, current smokers, smokers smoking both conventional and e-cigarettes, and e-cigarette smokers. The saliva samples were assessed for Interleukins (IL-1B, 6, 8, 10, and IL-1RA), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) using enzyme-linked immunosorbent assay. Plaque scores and Gingival Index, and body mass index were also calculated. Results: Statistically significant (P < 0.05) and remarkable relationship was seen in plaque scores and IL 1RA, 1 β, and 10 with the respective values as-0.285, 0.268, and 0.267. Regarding anti-inflammatory cytokines, CRP, IL-10, and IL-RA had the P-value of 0.073, 0.945, and 0.834 respectively. When these values were evaluated for proinflammatory cytokines, the P values were 0.0001, 0.019, 0.991, and 903 for TNF-α, IL-1 β, IL-6, and IL-8, respectively. These results were statistically significant for TNF-α (P = 0.001). Conclusion: Within its limitations, the present study concludes that smoking e-cigarettes whether solely or in combination with conventional smoking increases the levels of proinflammatory cytokines such as TNF-α and IL-1 β with decreased counter IL-1RA levels. [ABSTRACT FROM AUTHOR]