Background: The purpose of this study was to assess the effects of a comprehensive lifestyle intervention on modifiable cardiovascular risk factors among high-risk African Americans. Methods: The study included a randomized treatment/controlled intervention trial among 136 African Americans residing in Atlanta, GA who were overweight and had elevated blood pressure. The treatment group was exposed to 3-months of a multi-component intervention and the control to an abbreviated 6-week intervention after the completion of the treatment group’s intervention. The main outcomes included mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean waist circumference, mean body mass index (BMI), mean number of times exercise per week, mean number of servings of fruits and vegetables per day, and mean level of daily stress. Data were collected at baseline and at 6-month follow-up. Separate linear regressions were used with an established significance level of P < 0.05. Results: Results revealed significant net improvement in treatment group when compared to controls in waist circumference, BMI, times weekly exercise, servings of fruit and vegetables per day (P < 0.001, 0.04, 0.02, 0.002, respectively). Diastolic blood pressure also significantly improved within the treatment group for overall hypertensives from baseline to 6-month follow-up (90.9 mmHg to 83.1 mmHg, P = 0.002). Conclusion: These results show that a comprehensive lifestyle intervention can improve cardiovascular risk factor profile among high risk African Americans. Caregivers should encourage patients to participate in such programs and public health policymakers should allocate resources to community based health oriented organizations to implement comprehensive lifestyle program.