Purpose: The aim of the current study was to compare and contrast the effects of various smoking types. This study focused on traditional cigarettes, electronic cigarettes and heated tobacco products compared with non-smokers on the outcome of non-surgical treatment of moderate generalized periodontitis. Subjects and methods: The present study included a total of sixty (60) patients with moderate generalized chronic periodontitis. They were divided into four equivalent groups to be managed with non-surgical mechanical debridement. The clinical results of the study were evaluated using Plaque Index, Gingival Index, Pocket depth measurements, and Clinical attachment level. The clinical measurements were obtained at the baseline, 1 month, 3 months, and 6 months intervals. Samples of gingival crevicular fluid were collected from periodontal pockets at the site of periodontal treatment at the same intervals of clinical evaluation. The collected samples were analyzed for detection of interleukin 8 (IL8), and Tumor necrosis factor (TNF-α) levels. Results: Non-smoker group showed the best improvement of the clinical parameters and the lowest level of the inflammatory cytokines followed by the HTPs smokers then E-cigarette smokers'. Furthermore, traditional smokers showed the least improvement of the clinical parameters and highest level of the inflammatory cytokines. Conclusion: The present study revealed that different types of smoking affect the outcome of non-surgical periodontal therapy. Comparing between HTPs, vaping, and traditional smoking, HTPs have the least effect on periodontal therapy, vaping has the moderate effect and traditional smoking has the strongest effect.