This exploratory substudy of The Iron (Fe) and Atherosclerosis Study (FeAST) compared baseline inflammatory markers, including cytokines, C-reactive protein (CRP), and ferritin, in subjects with peripheral arterial disease (PAD) taking statins with subjects with PAD who were not taking statins. Inflammatory markers in the serum of 47 subjects with PAD not taking statins and a healthy cohort of 21 medication-free men were compared with 53 PAD subjects taking statins at entry to the FeAST. Healthy subjects demonstrated lower levels of tumor necrosis factor (TNF)-R1, interleukin-6 (IL-6), and CRP. TNF-alpha R1 averaged 2.28 ng/mL versus 3.52 ng/mL, p = .0025; IL-6 averaged 4.24 pg/mL versus 16.61 pg/mL, p = .0008; and CRP averaged 0.58 mg/dL versus 0.92 mg/dL, p = .0192. A higher level of IL-6 was observed in PAD statin takers versus PAD subjects not taking statins: 19.47 pg/mL versus 13.24 pg/mL, p = .0455. As expected, total cholesterol and low-density lipoprotein levels were lower in the statin-treated group, p = .0006 and p = .0001, respectively. No significant differences in inflammatory cytokines were detected for varying doses of simvastatin. Additionally, no significant differences in inflammatory biomedical markers were found in subjects with PAD alone compared with those with concomitant coronary artery disease (CAD). Unexpectedly, serum inflammatory cytokine IL-6 levels were significantly higher in PAD subjects receiving statins. There was no difference in measured inflammatory markers in PAD subjects with concomitant CAD.