Background: People experiencing financial burden are underrepresented in clinical trials. Objective: Describe the prevalence of cost-related considerations influential to trial participation and their associations with person-level characteristics. Design: This cross-sectional study used and assessed how three cost-related considerations would influence the decision to participate in a hypothetical clinical trial. Participants: A total of 3682 US adult respondents to the Health Information National Trends Survey Main Measures: Survey-weighted multivariable logistic regression estimated associations between respondent characteristics and odds of reporting cost-related considerations as very influential to participation. Key Results: Among 3682 respondents, median age was 48 (IQR 33–61). Most were non-Hispanic White (60%), living comfortably or getting by on their income (74%), with ≥ 1 medical condition (61%). Over half (55%) of respondents reported at least one cost-related consideration as very influential to trial participation, including if usual care was not covered by insurance (reported by 42%), payment for participation (24%), or support for participation (24%). Respondents who were younger (18–34 vs. ≥ 75, adjusted odds ratio [aOR] 4.3, 95% CI 2.3–8.1), more educated (high school vs.