Prospective studies supporting a relationship between elevated lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and incident peripheral arterial disease (PAD) are limited. We evaluated the association of Lp-PLA₂ with incident PAD in a multi-ethnic cohort without clinical cardiovascular disease. A total of 4622 participants with measurement of Lp-PLA₂ mass and Lp-PLA₂ activity and an ankle–brachial index (ABI) between 0.9 and 1.4 were followed for the development of PAD (median follow-up = 9.3 years), defined as an ABI <=0.9 and decline from baseline >=0.15. There were 158 incident PAD events during follow-up. In adjusted logistic regression models, each higher standard deviation of both Lp-PLA₂ activity and mass did not confer an increased risk of developing PAD [odds ratios, (95% confidence intervals)]: 0.92 (0.66–1.27) for Lp-PLA₂ activity and 1.06 (0.85–1.34) for mass. Additionally, no significant interaction was found according to ethnicity: p=0.43 for Lp-PLA₂ activity and p=0.55 for Lp-PLA₂ mass. We found no evidence of an association between Lp-PLA₂ and incident PAD.