Large samples of the general population are exposed to the possibility of being enrolled in clinical trials on preventive strategies. Because little information is available on the general population, data were collected on what Italians know and how they feel about clinical research and factors that might help implement measures to improve participation in the main phases of clinical research were assessed. A random sample of 950 citizens representative of the Italian population was interviewed by ad hoc trained interviewers, using a standardized questionnaire with seven multiple-choice questions and two scenarios. Participants' knowledge and opinions about clinical research were in general limited, attitudes toward participation in clinical studies were unsatisfactory, and the results varied significantly according to sociodemographic and geographic variables. These results give a description of the people's level of knowledge and attitude about clinical research in Italy and also clarify the importance of factors that may be related to the study's principal variables. These findings might be useful in helping design and implement effective interventions to improve people's participation in the main phases of clinical research.