Despite evidence-based recommendations for addressing obesity in the clinical setting, lifestyle interventions are lacking in practice. The objective of this study was to translate an evidence-based lifestyle program into the clinical setting by adapting it for delivery via the Internet. We adapted the Diabetes Prevention Program's lifestyle curriculum to an online format, comprising 16 weekly and 8 monthly lessons, and conducted a before-and-after pilot study of program implementation and feasibility. The program incorporates behavioral tools such as e-mail prompts for online self-monitoring of diet, physical activity, and weight, and automated weekly progress reports. Electronic counseling provides further support. Physician referral, automated progress reports, and as-needed communication with lifestyle coaches integrate the intervention with clinical care. We enrolled 50 patients from a large academic general internal practice into a pilot program between November 16, 2006 and February 11, 2007. Patients with a body mass index (BMI) =25 kg/m2, at least one weight-related cardiovascular risk factor, and Internet access were eligible if referring physicians felt the lifestyle goals were safe and medically appropriate. Participants were primarily female (76%), with an average age of 51.94 (standard deviation [SD] 10.82), and BMI of 36.43 (SD 6.78). At 12 months of enrollment, 50% of participants had logged in within 30 days. On average, completers (n = 45) lost 4.79 (SD 8.55) kg. Systolic blood pressure dropped 7.33 (SD 11.36) mm Hg, and diastolic blood pressure changed minimally (+0.44 mm Hg; SD 9.27). An Internet-based lifestyle intervention may overcome significant barriers to preventive counseling and facilitate the incorporation of evidence-based lifestyle interventions into primary care.