OBJECTIVE To study the effects of age, race, years of contact lens wear, and degree of myopia on endothelial cell density, the coefficient of variation, and the percentage of hexagonal cells. METHODS A total of 149 subjects with a broad variation in age (19 to 71 years), refractive error (39.6% had myopia over -5.00 D), and contact lens history (13.4% had >20 years of wear) were examined. Most subjects were white, but one third were Asian. The Konan specular microscope was used to capture images from 1 eye of each subject and analyzed with the KSS-300 software. Multiple regression analysis was used to build models of endothelial cell density, polymegathism, and pleomorphism. RESULTS Age and race significantly affected endothelial cell density (ECD = 3274 - 12.7 x Age + [164 if Asian]). Years of contact lens wear, age, and their interaction significantly affected coefficient of variation (CoV = 24.3 + 0.72 x CLyears + 0.18 x Age - 0.011 x interaction). Years of contact lens wear, age, and refractive error all independently affected the percentage of hexagonal cells (% Hex = 70 - 0.29 x CLyears - 0.21 x Age + 0.4 x Rx). CONCLUSIONS The three key aspects of corneal endothelial morphology are influenced by different factors. Any impact of contact lens wear on endothelial cell density may be caused by the confounding effect of age, and refractive error was associated with the percentage of hexagonal cells. Therefore, in studying the influence of drugs, devices, or disease, it is important to control for several subject-related factors.