There is little information on the progression of peripheral arterial disease (PAD) over time. A series of 508 patients with a prior examination for PAD were contacted and brought in for follow-up to evaluate the natural history of PAD. A total of 85 patients were excluded because they had interventions in both limbs prior to their return visit. Progression was assessed in the remaining 423 patients for a total of 755 limbs, both quantitatively and qualitatively using six categories of PAD severity. There was a modest overall categorical progression of disease: 228 limbs (30.2%) displayed categorical progression, while 172 limbs (22.8%) improved over a 4.6-year average follow-up. Through analysis of quantitative change, it was determined that more quantitative progression occurred than was evident from categorical progression. Two of the three non-invasive tests employed, the ankle/brachial index (ABI) and posterior tibial peak forward flow velocity (peak PT), showed statistically significant progression during follow-up: mean ABI change = -0.019, 95% confidence interval (CI)= -0.031 to -0.007; mean peak PT change = -2.32 cm/s, 95% CI = -3.20 to -1.44. The toe/brachial index (TBI) also suggested progression: mean change= -0.013, but the 95% CI included no change. Standard scores (sum of the Z-scores for ABI, peak PT and TBI) were calculated. The standard score progressed approximately 0.34 units (standard deviations), p-value <0.001, over 4.6 years; or about 0.07 standard deviations per year. There were independent and statistically significant (p<0.05) associations between the rate of PAD progression (standard score change) and age, diabetes, classic ('Rose') intermittent claudication, moderate to severe PAD in the same limb, moderate to severe PAD in the contralateral limb and future therapeutic intervention. There were independent and suggestive associations (0.05<p-value<0.15) between PAD progression and pain at rest, mild PAD in the same limb, and mild PAD in the contralateral limb. PAD progression was not associated with gender, atypical claudication, or amputation status. Thus, in this cohort of PAD patients, PAD on average progressed significantly over 4.6 years. This progression was independently related to age, diabetes and several markers of disease severity.