Men and women with lower extremity peripheral arterial disease (PAD) have reduced physical activity levels compared with persons without PAD. We describe associations between physical activity levels with D-dimer, pro-coagulant factors, and inflammatory markers in patients with PAD. Participants were 188 patients with PAD identified from non-invasive vascular laboratories. Physical activity was measured over 7 days with a vertical accelerometer. We measured the ankle-brachial index (ABI) and levels of D-dimer, C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA), prothrombin 1.2, t-PA antigen, PAI-1, and the t-PA antigen/PAI-1 ratio. Adjusting for age, sex, race, body mass index, ABI, comorbidities, smoking, total cholesterol/HDL ratio and statin use (for CRP only), we found significant inverse linear associations between physical activity levels and log D-dimer (p = 0.002), log CRP (p < 0.001), fibrinogen (p = 0.014), and log SAA (p = 0.012). There were no significant associations between physical activity levels and other blood factors. In an analysis adjusting for all blood factors simultaneously along with known and potential confounders, log D-dimer was the only blood factor associated significantly with physical activity levels (p = 0.036). Based on these findings, future studies should assess whether interventions to increase physical activity in patients with PAD reduce levels of D-dimer and inflammatory markers.