: The success of clinical trials hinges on the effective recruitment and retention of participants, which remains a persistent challenge. Smoking has well-documented adverse effects on health and is a significant predictor of various chronic diseases. However, smoking status impact on the motivation to participate in clinical trials is less clear. : This cross-sectional study, utilizing data from the Health Information National Trends Survey (HINTS) 5 Cycle 4 with a sample of 3793 participants, investigates how smoking status (current, former, and never smoker) influences motivation to participate in clinical trials using a structural equation model. Key predictors of trial participation include age, gender, education level, race/ethnicity, income, ethnicity, depression, and chronic respiratory conditions. : In the overall sample, 51.2% of the participants were females, 76.0% were White adults, 83.1% were non-Hispanic, 39.0% had some college education, and 42.5% had a household income of $75,000 or more. The mean age of the participants was 48.4 years, and the mean depression score was 2.2. Structural equation model results showed a significant positive association between female gender and motivation in clinical trial participation for current smokers. For former smokers, older age and Hispanic ethnicity showed negative associations, while education showed a positive association. For those who have never smoked, older age and other races showed negative associations. : This study highlights the significant role of education, age, gender, and race/ethnicity among people with different smoking statuses in motivating clinical trial participation. Tailored strategies that address these barriers are essential for improving recruitment and retention in tobacco cessation trials.
