This cross-sectional study was set in an academic medical center and conducted to identify associations of physical activity level and walking exercise frequency with calf skeletal muscle characteristics in individuals with lower extremity peripheral arterial disease (PAD). Calf muscle characteristics in 439 men and women with PAD were measured with computed tomography at 66.67% of the distance between the distal and proximal tibia. Physical activity was measured continuously during 7 days with a vertical accelerometer. Patient report was used to determine the number of blocks walked during the past week and walking exercise frequency. Results were adjusted for age, sex, race, comorbidities, ankle-brachial index, body mass index, smoking, and other confounders. For both objective and subjective measures, more physically active PAD participants had higher calf muscle area and muscle density. Calf muscle area across tertiles of accelerometer-measured physical activity were first activity tertile, 5071 mm(2); second activity tertile: 5612 mm(2); and third activity tertile, 5869 mm(2) (P < .001). Calf muscle density across tertiles of patient-reported blocks walked during the past week were first activity tertile, 31.4 mg/cm(3); second activity tertile, 33.0 mg/cm(3); and third activity tertile, 33.8 mg/cm(3) (P < .001). No significant associations were found between walking exercise frequency and calf muscle characteristics. Among participants with PAD, higher physical activity levels, measured by accelerometer and by patient-reported blocks walked per week, were associated with more favorable calf muscle characteristics. In contrast, more frequent patient-reported walking exercise was not associated with more or less favorable calf muscle characteristics. Results suggest that clinicians should encourage their patients to increase their walking activity during daily life.