Previous animal studies have demonstrated that phthalate exposure is associated with depression-like behaviors. However, no human study has explored this relationship. We explored the association between urinary phthalate metabolite concentrations and depression in a nationally representative sample of the U.S. elderly population. We analyzed 2030 participants aged 60 years or older with available data on phthalates and depression from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). We selected 10 urinary phthalate metabolites with a weighted detection rate >60%. Depression was defined as a 9-item Patient Health Questionnaire score ≥10. The models were adjusted for age, sex, race/ethnicity, education level, income-to-poverty ratio, health insurance coverage, marital status, smoking status, alcohol consumption, moderate physical activity, body mass index, comorbidity status, NHANEs cycle, and urinary creatinine levels. One-unit increases in log-transformed mono-(3-carboxypropyl) phthalate (MCPP) (odds ratio [OR]=1.24, 95% confidence interval [CI]=1.02-1.52) and mono(carboxynonyl) phthalate (MCNP) (OR=1.42, 95% CI=1.15-1.75) were positively associated with depression. When we stratified the urinary phthalate metabolites into quartiles, the highest quartiles (Q4) of MCNP (OR=2.57, 95% CI=1.25-5.27) and mono-n-butyl phthalate (MBP) (OR=2.40, 95% CI=1.10-5.22) were associated with depression compared with the lowest quartiles (Q1). Concentrations of urinary phthalate metabolites MCPP, MCNP, and MBP were positively associated with the risk of depression in a representative sample of the U.S. elderly population. However, the present cross-sectional study is hypothesis generating and the associations need to be investigated through further longitudinal studies.