Purpose: This study examined the associations between participant and site characteristics and retention in a multisite cardiovascular disease risk reduction project. Design and Methods: Data were derived from the Special Diabetes Program for Indians Healthy Heart Demonstration Project, an intervention to reduce cardiovascular risk among American Indians and Alaska Natives with diabetes. In 2006, a total of 1,072 participants from 30 participating sites completed baseline questionnaires measuring demographics and sociobehavioral factors. They also underwent a medical examination at baseline and were reassessed annually after baseline. A Provider Annual Questionnaire was administered to staff members of each grantee site at the end of each year to assess site characteristics. Generalized estimating equation models were used to evaluate the relationships between participant and site characteristics and retention 1 year after baseline. Results: Among enrolled participants, 792 (74%) completed their first annual assessment. Participants who completed the first annual assessment tended to be older and had, at baseline, higher body mass index and higher level of physical activity. Site characteristics associated with retention included average age of staff, proportion of female staff members, and percentage of staff members having completed graduate or professional school. Implications: Understanding successful retention must reach beyond individual characteristics of participants to include features of the settings that house the interventions.