Objective.Local inflammation plays a prominent role in osteoarthritis (OA). This could be reflected in the presence of elevated soluble inflammatory markers. We conducted analyses to assess the association of inflammatory markers with radiographic OA of the hands and knees in a large community-based cohort.Methods.The Framingham Offspring cohort consists of the adult children of the original cohort and their spouses. In 1998–2001 these subjects provided blood specimens that were tested for 17 markers of systemic inflammation. In 2002–2005 these subjects had radiographs of both knees and hands. Each hand and knee joint was assigned a Kellgren and Lawrence (KL) score (0–4). We used logistic regression with generalized estimating equations and adjustment for age, sex, and body mass index to examine the association between each inflammatory marker and the presence of radiographic OA (ROA = KL grade ≥ 2) in any joint. We also constructed models for hand joints and knee joints alone.Results.Radiographs and measures of inflammation were done for 1235 subjects (56% women, mean age 65 yrs). Of that group, 729 subjects (59%) had ROA in ≥ 1 hand or knee joint: 179 (14.3%) had knee OA, and 694 (56.2%) had hand OA. There were no significant associations between any marker of inflammation and ROA.Conclusion.In this large sample, in which OA was carefully assessed and multiple markers measured, we found no evidence of an association between any inflammatory marker and the presence of radiographic OA.