BACKGROUND: Numerous epidemiologic studies have identified obesity as a vital risk factor for the development of colorectal cancer (CRC). More recently, obesity has been linked to the development of colorectal adenomatous polyps (adenomas), the precursor lesion of up to 80% of CRCs. The extent to which weight loss could reduce risk in obese patients is unclear. PROPOSED PROJECT: The proposed study is a randomized clinical trial that aims to evaluate the relationship between weight reduction and the prevalence of recurrent (metachronous) adenomas among obese patients in a safety-net health care setting. The intervention group will participate in a comprehensive, individually structured weight loss program in order to achieve successful long-term weight loss. The control group will receive no special recommendations about weight loss other than as part of “usual care”. Anthropometric measures (weight in kilograms [kg], height in meters squared [m2] and body mass index [BMI]) will be monitored annually until the time of surveillance colonoscopy which will occur in accordance with the U.S. Multi-Society Task Force recommendations. Statistical methods will be used to compare rates of recurrent adenomas among the two study groups after adjustments for duration of follow-up and potential confounders. CONCLUSION/SIGNIFICANCE: The results of this study will provide new evidence to support weight reduction as a preventive strategy for reducing CRC risk among obese patients.