Smoking has a profound effect on platelet morphology and activation and has also been shown to affect hemostasis, coagulation, and healing cascade. To date, no previous reports are available to assess the impact of cigarette smoke on leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) membranes. Therefore, this study aims to analyze the impact of cigarette smoking on the mechanical and biologic properties of L-PRF and A-PRF membranes. Sixty blood samples from both smokers (n = 34) and nonsmokers (n = 26) who were matched for age and other factors were collected and subjected to complete blood count and platelet indices (mean platelet volume, platelet distribution width, platelet large cell ratio, and plateletcrit). The L-PRF membrane (2,700 rpm; 12 minutes) and A-PRF membrane (1,500 rpm; 14 minutes) were prepared using a standard protocol. A total of 64 experimental L-PRF and A-PRF membranes from 16 individuals selected randomly from the two groups were subjected to tensile strength evaluation using a micro universal testing machine and growth factor release analysis (platelet-derived growth factor [PDGF-AB], vascular endothelial growth factor [VEGF], and bone morphogenic protein-2 [BMP-2]) using ELISA (enzyme-linked immune sorbent assay). Results were tabulated, and statistical analysis was done using Mann-Whitney, Kruskal-Wallis, and Spearman correlation tests. Tensile strengths of L-PRF and A-PRF did not show a statistical difference between groups (P = .47). BMP-2 was not detected in any of the groups. A high initial release of PDGF-AB and VEGF was noticed in A-PRF samples from smokers. Although statistically insignificant, cigarette smoking does affect platelet activation and influences the tensile strength of L-PRF membranes as well as growth factor release in A-PRF membranes in smokers.