Osteoarthritis (OA) and cardiovascular disease (CVD) share age and obesity as risk factors, but may also be linked by pathogenic mechanisms involving metabolic abnormalities and systemic inflammation. This study compared the prevalence of OA and metabolic syndrome (MetS) in subjects with OA versus the general population without OA to determine whether having OA predicts increased cardiovascular risk. National Health and Nutrition Examination Survey III data were used as a representative sample of the general US population. Subjects included adults aged > or = 18 years with records of history, physical, radiographic, and laboratory data adequate to assess for diagnoses of MetS and OA. Logistic regression was used to examine the association between MetS and population-weighted variables. The general population sample included 7714 subjects (weighted value representing 174.9 million population), of whom 975 subjects had OA (weighted value 17.5 million) and 6739 did not (weighted value 157.4 million). Metabolic syndrome was prevalent in 59% of the OA population and 23% of the population without OA. Each of the 5 cardiovascular risk factors that comprise MetS was more prevalent in the OA population versus the population without OA: hypertension (75% vs 38%), abdominal obesity (63% vs 38%), hyperglycemia (30% vs 13%), elevated triglycerides (47% vs 32%), and low high-density lipoprotein cholesterol (44% vs 38%). Metabolic syndrome was more prevalent in subjects with OA regardless of sex or race. The association between OA and MetS was greater in younger subjects and diminished with increasing age. Having OA at age 43.8 years (mean age of the general population) was associated with a 5.26-fold (SE = 1.58, P < 0.001) increased risk of MetS. This association remained strong when obesity was controlled for in additional regression models. Osteoarthritis is associated with an increased prevalence of MetS, particularly in younger individuals. Global cardiovascular risk should be assessed in individuals aged < or = 65 years with OA, and should be considered when prescribing analgesics for OA patients.