Surgical models have best shown the relationship between ankle and midfoot osteoarthritis, although findings regarding the calcaneocuboid joint have varied. To the authors' knowledge, no studies have evaluated the relationship between degenerative changes across the tibiotalar and calcaneocuboid joints. The goal of this study was to determine whether such a relationship exists and which joint degenerates first. A single examiner evaluated 694 tibiotalar and calcaneocuboid joints to determine the presence of osteoarthritis. Multiple linear regression analysis was conducted with a standard P value cutoff (P<.05) and 95% confidence interval. The average incidence of tibiotalar and calcaneocuboid osteoarthritis in specimens older than 40 years was compared with the incidence in those 40 years and younger. A positive correlation between tibiotalar and calcaneocuboid osteoarthritis was noted. African-American subjects were less likely than white subjects to have tibiotalar osteoarthritis. The finding of right and left tibiotalar and calcaneocuboid osteoarthritis in subjects 40 years and younger showed that midfoot arthritis was significantly more common than arthritis of the ankle. The prevalence of calcaneocuboid osteoarthritis remains stable after 40 years of age, and the prevalence of tibiotalar osteoarthritis approaches that of calcaneocuboid osteoarthritis. Calcaneocuboid osteoarthritis precedes tibiotalar osteoarthritis. Altered biomechanics involved in calcaneocuboid osteoarthritis are transferred to the tibiotalar joint, leading to tibiotalar osteoarthritis as the subject ages. Early education, surveillance, physical therapy, shoe adjustment, and orthotics may help to reduce the forces across the midfoot and prevent ankle arthritis in the long term.