A comprehensive and systematic assessment of disability and mortality due to lower extremity peripheral artery disease (PAD) is lacking. Therefore, we estimated PAD deaths, disability-adjusted life years (DALYs), and years of life lost in 21 regions worldwide for 1990 and 2010. We used the GBD (Global Burden of Diseases 2010) study causes of death database, and the cause of death ensemble modeling approach to assess levels and trends of PAD deaths and years of life lost over time, by age, sex, and region. Assessment of DALYs employed estimates of PAD prevalence from systematic reviews of epidemiologic data using a Bayesian meta-regression method. In 1990, the age-specific PAD death rate per 100,000 population ranged from 0.05 (95% confidence interval [CI]: 0.03 to 0.09) among those 40 to 44 years old to 16.63 (95% CI: 10.47 to 25.31) among the 80+ years group. In 2010, the corresponding estimates were 0.07 (95% CI: 0.04 to 0.13) and 28.71 (95% CI: 18.3 to 43.06). Death rates increased consistently with age in 1990 and 2010, and the rates in 2010 were higher than they were in 1990 in all age categories. The largest relative change in median death rate of +6.03 per 100,000 (95% CI: 1.50 to 11.85) was noted in the Asia Pacific-High Income region and was largely driven by higher rates in women: +17.36 (95% CI: 1.79 to 32.01) versus +1.25 (95% CI: 0.13 to 2.39) in men. The overall relative change in median DALYs was larger in developing nations than in developed nations: 1.15 (95% CI: 0.80 to 1.66) versus 0.77 (95% CI: 0.55 to 1.08). Of note, the overall relative change in median DALYs was higher among both men and women in developing versus developed countries: men: 1.18 (95% CI: 0.82 to 1.65) versus 0.51 (95% CI: 0.30 to 0.81), and women: 1.11 (95% CI: 0.58 to 2.02) versus 1 (95% CI: 0.67 to 1.47). Within developed nations, the overall relative change in median DALY rates was larger in women than in men: +1.00 (95% CI: 0.67 to 1.47) versus +0.51 (95% CI: 0.3 to 0.81). Similarly, the overall relative change in median years of life lost rate in developed countries was larger in women than in men: +1.64 (95% CI: 1.17 to 2.34) versus +0.53 (95% CI: 0.24 to 0.94). The relative increases in median years lived with nonfatal disease disability (YLD) rates in men and women were larger in developing versus developed nations: men: 0.87 (95% CI: 0.59 to 1.2) versus 0.49 (95% CI: 0.29 to 0.73), and women: 0.75 (95% CI: 0.46 to 1.09) versus 0.49 (95% CI: 0.29 to 0.73). Disability and mortality associated with PAD has increased over the last 20 years, and this increase in burden has been greater among women than among men. In addition, the burden of PAD is no longer confined to the elderly population, but now involves young adults. Furthermore, the relative increase in PAD burden in developing regions of the world is striking and exceeds the increases in developed nations. © 2014 World Heart Federation (Geneva). Published by Elsevier Ltd. All rights reserved.