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BACKGROUND Diverse smoking trajectories may influence cytokine expression after non-surgical periodontal therapy and supportive periodontal care. Thus, we aimed to describe cytokine profiles in periodontal healing after periodontal therapy in smokers. MATERIALS AND METHODS A smoking cessation program and non-surgical periodontal therapy were offered to 80 smokers with periodontitis. Smoking trajectories (quitters/light, moderate, heavy) were observed. The association of salivary interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ, and TNF-α with smoking trajectories and periodontal outcomes was determined using mixed-effects linear regression. RESULTS Among quitters/light smokers, IL-1β was associated with an increase in mean periodontal pocket depth (PPD) and mean clinical attachment level (CAL). IL-6 was associated with a decrease in mean PPD and CAL in heavy smokers, whereas IL-8 was associated with a decrease in PPD among moderate smokers. TNFα was associated with a reduction in mean PPD and CAL among quitters/light smokers, while among moderate smokers, TNFα was associated with an increase in mean PPD and CAL. IL-12 and IL-13 were associated with a decrease in mean PPD in moderate smokers. CONCLUSION Our findings suggest that distinctive smoking exposures induce differential cytokine expression, which, in turn, seems to influence periodontal repair. This article is protected by copyright. All rights reserved.