In this study we assessed the utility of self-reported cognitive function using two PROMIS® Cognitive Function (PROMIS-CF) items in an observational clinical sample of patients aged 65 and older (n = 16,249) at a large health system. We evaluated the association of PROMIS-CF scores with clinical characteristics and Montreal Cognitive Assessment (MoCA) scores, and we used logistic regression to examine predictors of 1-year decline in PROMIS-CF scores among patients with available data. PROMIS-CF scores were associated with clinical characteristics as hypothesized, with lower (more impaired) scores for patients with cognitive impairment (CI) diagnoses, multiple comorbidities, and those taking cognitive enhancing or interfering medications. PROMIS-CF scores were also positively associated with MoCA scores. Predictors of 1-year decline in PROMIS-CF scores included CI diagnoses, use of cognitive enhancing medications, higher depression scores, and lower social role function. Our findings suggest potential utility of PROMIS-CF items in a brief patient-administered screening tool for CI.