Adults with limited health literacy have difficulty managing chronic conditions, higher hospitalization rates, and more healthcare expenditures. Simple screening tools have been developed, but limited work has evaluated instruments among low-income populations. This study assessed health literacy among primary care patients of a federally qualified health center, and compared a single screening question about perceived difficulty completing medical forms.A cross-sectional survey was administered to English-speaking patients ≥40 years. Both the Newest Vital Sign (NVS), a 6-item questionnaire, and a single-item screening question about perceived difficulty with completing medical forms, assessed health literacy. Logistic regression was used to identify predictors of inadequate health literacy and receiver operator curves compared the NVS and single-item question.Participants (n = 406) were, on average, aged 58.5 years (±11.3), 72.2% female, and identified as Hispanic/Latino (19.2%), non-Hispanic white (31.0%), non-Hispanic black (40.9%), or other (8.9%). Of the 406 participants, 335 (82.5%) completed the NVS. Patients who declined NVS were more likely to be older (P < .001) and male (P = .01). Only 13.7% had adequate health literacy. Older adults, Hispanic and non-Hispanic black patients, patients with missed office visits, and those reporting less confidence completing medical forms were significantly more likely to have inadequate health literacy. Perceived confidence completing medical forms demonstrated low sensitivity but high specificity at multiple thresholds.This is the first investigation to compare the NVS and confidence completing medical forms question. Many patients declined health literacy assessments, but health literacy screening may identify patients who need additional health education and resources.