The purpose of this study was to estimate the total medical expenditures attributable to physical inactivity patterns among members of a large health plan, Blue Cross Blue Shield of Minnesota. The study used a cost-of-illness approach to attribute medical and pharmacy costs for specific diseases to physical inactivity in 2000. Relative risks come from the scientific literature, demonstrating that heart disease, stroke, hypertension, type 2 diabetes, colon cancer, breast cancer, osteoporosis, depression, and anxiety are directly related to individual physical activity patterns in adults. Data sources were the 2000 Behavioral Risk Factor Surveillance System and medical claims incurred in 2000 among 1.5 million health plan members aged ≥18 years. Primary analysis was completed in 2002. Nearly 12% of depression and anxiety and 31% of colon cancer, heart disease, osteoporosis, and stroke cases were attributable to physical inactivity. Heart disease was the most expensive outcome of physical inactivity within the health plan population, costing $35.3 million in 2000. Total health plan expenditures attributable to physical inactivity were $83.6 million, or $56 per member. This study confirms the growing body of research quantifying physical inactivity as a serious and expensive public health problem. The costs associated with physical inactivity are borne by taxpayers, employers, and individuals in the form of higher taxes to subsidize public insurance programs and increased health insurance premiums.