The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F 2α (PGF 2α ) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF 2α (a major metabolite of PGF 2α ), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF 2α (an F 2 -isoprostane, indicator of oxidative stress), and serum α-tocopherol were quantified in a population-based sample (n=642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF 2α , P<0.001; IL-6, P=0.01) than non-smokers. 8-iso-PGF 2α was increased (P<0.01) and α-tocopherol reduced (P<0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF 2α , IL-6 and 8-iso-PGF 2α compared non-smokers. This is the first study to show that smokers have increased PGF 2α formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.