There is much attention to recruitment of diverse populations in research, but little is known about the influence of health literacy and numeracy skills. To determine if health literacy and numeracy affect individuals' interest to participate in research studies. Cross-sectional survey data were pooled from 3 large studies conducted in the Mid-South Clinical Data Research Network. Adult patients enrolled in 1 of 3 Mid-South Clinical Data Research Network studies. The survey domains included

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... ographic items, the 3-item Brief Health Literacy Screen (range 3-15), and the 3-item Subjective Numeracy Scale (range 3-18). The outcome was a sum index measure of a 7-item instrument (range 7-21) assessing individuals' interest in participating in different types of research, including research that involves taking surveys, giving a blood sample, participating via phone or internet, taking an investigational medication, meeting at a local community center or school, including family, or staying overnight at a hospital. Respondents (N = 15,973) were predominately women (65.5%), White (81.4%), and middle aged (M = 52.8 years, SD = 16.5); 32.4% previously participated in research. Self-reported health literacy was relatively high (M = 13.5 out of 15, SD = 2.1), and subjective numeracy skills were somewhat lower (M = 14.3 out of 18, SD = 3.6). After adjustment for age, gender, race, income, education, and other characteristics, lower health literacy and numeracy skills were each independently associated with less interest in research participation (p < 0.001 for each). Prior research participation was associated with greater interest in future research participation (p < 0.001). After adjustment for factors known to be predictive of interest, individuals with lower health literacy or numeracy scores were less interested in participating in research. Additional work is needed to elucidate reasons for this finding and to determine strategies to engage these populations.