Objectives: To compare the corneal endothelial morphology and cell density of diabetic smokers and non-smokers with 50–70 age-matched healthy subjects and to determine whether smoking increases the effects of type 2 diabetes mellitus (DM) on these corneal parameters. Patients and Methods: This prospective cohort study included 200 patients who were assigned to four groups, including smokers with type 2 DM (group 1), nonsmokers with type 2 DM (group 2), healthy smokers (group 3), and healthy nonsmokers (control group, group 4). Noncontact specular microscopy was used to measure central endothelial cell density (ECD), coefficient of variation of cell area (CV), percentage of hexagonal cells (HEX), and central corneal pachymetry (CCT). Results: According to the ECD and CCT values (P < 0.001 and P = 0.013, respectively), a significant difference was observed between the groups. The mean ECD was lowest in diabetic smokers (1917 ± 399 cells/mm2 ). Healthy smokers and diabetic smokers had significantly lower ECD compared to the control group (P = 0.03 and P < 0.001, respectively). Healthy smokers and diabetic smokers had significantly lower ECD compared to diabetic nonsmokers (P = 0.012 and P < 0.001, respectively). The cornea was significantly thicker in the diabetic smokers than in the control group (P = 0.013). Conclusion: The coexistence of DM and smoking causes a significant decrease in ECD and an increase in CCT. Cigarette smoking is more harmful to corneal endothelial cells than DM alone. Keywords:Objectives: To compare the corneal endothelial morphology and cell density of diabetic smokers and non-smokers with 50–70 age-matched healthy subjects and to determine whether smoking increases the effects of type 2 diabetes mellitus (DM) on these corneal parameters. Patients and Methods: This prospective cohort study included 200 patients who were assigned to four groups, including smokers with type 2 DM (group 1), nonsmokers with type 2 DM (group 2), healthy smokers (group 3), and healthy nonsmokers (control group, group 4). Noncontact specular microscopy was used to measure central endothelial cell density (ECD), coefficient of variation of cell area (CV), percentage of hexagonal cells (HEX), and central corneal pachymetry (CCT). Results: According to the ECD and CCT values (P < 0.001 and P = 0.013, respectively), a significant difference was observed between the groups. The mean ECD was lowest in diabetic smokers (1917 ± 399 cells/mm2 ). Healthy smokers and diabetic smokers had significantly lower ECD compared to the control group (P = 0.03 and P < 0.001, respectively). Healthy smokers and diabetic smokers had significantly lower ECD compared to diabetic nonsmokers (P = 0.012 and P < 0.001, respectively). The cornea was significantly thicker in the diabetic smokers than in the control group (P = 0.013). Conclusion: The coexistence of DM and smoking causes a significant decrease in ECD and an increase in CCT. Cigarette smoking is more harmful to corneal endothelial cells than DM alone.