Most Western chronic diseases are closely tied to lifestyle behaviors, and many are preventable. Despite the well-distributed knowledge of these detrimental behaviors, effective efforts in disease prevention have been lacking. Many of these chronic diseases are related to obesity and type 2 diabetes, which have doubled in incidence during the last 35 years. The Complete Health Improvement Program (CHIP) is a community-based, comprehensive lifestyle modification approach to health that has shown success in addressing this problem. This pilot study demonstrates the effectiveness of CHIP in an underserved, rural, and vulnerable Appalachian population. Two hundred fourteen participants in CHIP collectively demonstrated significant reductions in body mass index, systolic and diastolic blood pressure, and fasting blood levels of total cholesterol, low-density lipoprotein, and glucose. If these results can be repeated in other at-risk populations, CHIP has the potential to help reduce the burden of preventable and treatable chronic diseases efficiently and cost-effectively.