Previous research has not examined the effect of health literacy on research subjects' completion of scheduled research follow-up. This article evaluates patient factors associated with incomplete research follow-up at three time points after enrollment in a large, hospital-based prospective cohort study. Predictor variables included health literacy, age, race, gender, education, employment status, difficulty paying bills, hospital diagnosis, length of stay, self-reported global health status, depression, perceived health competence, medication adherence, and health care system distrust. In a sample of 2,042 patients, multivariable models demonstrated that lower health literacy and younger age were significantly associated with a lower likelihood of completing research follow-up interviews at 2-3 days, 30 days, and 90 days after hospital discharge. In addition, patients who had less education, were currently employed, and had moderate financial stress were less likely to complete 90-day follow-up. This study is the first to demonstrate that lower health literacy is a significant predictor of incomplete research follow-up.