The objective of this study was to analyze the psychometric properties of the English and Spanish S-TOFHLA for three patient populations of interest. Despite being widely used, little is written about psychometric properties of the S-TOFHLA, particularly the Spanish version. Participants were Medicaid and Medicare patients: 936 non-Hispanic and 368 Hispanic patients completed the English S-TOFHLA; 1066 Hispanics completed the Spanish S-TOFHLA. Validity of both versions of the S-TOFHLA was supported by strong positive relationships with education and inverse relationships with age. Significant differences between scores for men and women remained after adjusting for level of education. Score differences occurred across numerous items. More research is needed on the S-TOFHLA and other health literacy instruments to determine why women score differently than men. Variability in literacy skills within subgroups of patients highlights the importance of healthcare providers being sensitive to patients' literacy levels in both spoken and written communications.