Retention of participants for intervention and follow-up activities is critical in cancer chemoprevention trials. Little has been published about retention patterns and predictors of retention in prevention studies. The Carotene and Retinol Efficacy Trial (CARET) provides an opportunity to study retention of volunteer participants in a large, long-term clinical trial. Two pilot studies were conducted in different populations to test the feasibility of critical strategies for the long-term study. Thirteen percent of the asbestos-exposed workers and 18% of the smokers became inactive during the pilot study. Of those remaining active, all but 2% of asbestos-exposed workers pilot study participants and 5% of smokers pilot study participants chose to participate in the full-scale efficacy trial. Five baseline predictors of inactivity for the asbestos-exposed participants emerged: being non-White, being a current smoker, having a history of high blood pressure at baseline, reporting two or more increases in symptoms during the placebo run-in, and having higher baseline levels of negative mental health measures (i.e. anxiety, depression, and fatigue). The only significant predictor of inactivity for smoker pilot participants was reporting symptoms during the placebo run-in. The most frequently reported reasons for becoming inactive during the pilot studies were general health issues and problems and symptoms that were seen as specific to the CARET vitamins. These findings suggest areas that could be tested to optimize retention in clinical trials.