BACKGROUND: To investigate the relationship between physical activity and risk of all-cause and cardiovascular disease (CVD) mortality in patients with peripheral artery disease (PAD). METHODS: We recruited 561 PAD cases of National Health and Nutrition Examination Survey from 1999 to 2004 and linked mortality data through December 31, 2019. We explored the effect of aerobic physical activity and muscle-strengthening activity on the risk of all-cause and CVD mortality employing cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) from 1999 to 2019. RESULTS: During an average of 9.8-year follow-up, a total of 435 deaths from all causes of the 561 PAD patients were recorded including 165 CVD deaths. Meeting the guidelines about physical activity released by World Health Organization in 2020 is not related to a lower risk for mortality in PAD patients. PAD patients engaging in moderate-to-vigorous intensity aerobic physical activity (MVPA) ≥ 60 min/week exhibited a significantly 45% (HR = 0.55; 95% CI = 0.37-0.85; P < 0.001) lower all-cause mortality risk and 60% (HR = 0.40; 95% CI = 0.27-0.70; P < 0.001) lower CVD mortality risk. PAD patients reached their maximal survival benefit of HR at 120-239 min/week of MVPA. The survival benefit of aerobic physical activity was notably greater in men and age < 65 years. Furthermore, PAD patients with muscle-strengthening activity 1-4 times/week had a 66% reduction risk of CVD mortality (HR = 0.34; 95% CI = 0.17-0.90; P = 0.011). CONCLUSIONS: Aerobic physical activity (MVPA ≥ 60 min/week) decreases the all-cause and CVD mortality risk among PAD patients. Muscle-strengthening activity (1-4 times/week) may provide survival benefits of CVD mortality in PAD patients.