Samuel Preston's major research interest is in the health of populations. He has written primarily about mortality trends and patterns in large aggregates, including mortality transitions and racial mortality differentials in the United States. Recent research has focused on the mortality effects of cigarette smoking and obesity in developed countries. With Irma Elo and past and present graduate students at Penn, he is helping to identify and understand the basis of regional inequalities in life expectancy in the United States. He is an author, with Michel Guillot and Patrick Heuveline, of the leading textbook in demography. He is a member of the National Academy of Science and the National Academy of Medicine.