Although there are efficacious weight loss interventions that can improve health and delay onset of diabetes and hypertension, these interventions have not been translated into clinical practice. The primary objective of this study is to evaluate the effectiveness and cost effectiveness of a tailored lifestyle intervention in primary care patients. Patients were recruited by their primary care physicians and eligible participants were randomized to an enhanced intervention or standard intervention. All participants met with a lifestyle counselor to set calorie and physical activity goals and to discuss behavioral strategies at baseline, 6 and 12 months. During the first year, enhanced intervention participants receive monthly counseling phone calls to assist in attaining and maintaining their goals. Enhanced intervention participants also receive weekly mailings consisting of tailored and non-tailored print materials and videos focusing on weight loss, physical activity promotion and healthy eating. The second year focuses on maintenance with enhanced intervention participants receiving tailored and non-tailored print materials and videos regularly throughout the year. Standard intervention participants receive five informational handouts on weight loss across the two years. This enhanced intervention that consists of multiple modalities of print, telephone, and video with limited face-to-face counseling holds promise for being effective for encouraging weight loss, increasing physical activity and healthy eating, and also for being cost effective and generalizable for wide clinical use. This study will fill an important gap in our knowledge regarding the translation and dissemination of research from efficacy studies to best practices in clinical settings.