Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F₂α (PGF₂α; as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF₂α (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF₂α as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF₂α levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.