Abstract—National guidelines for the prevention and treatment of hypertension recommend sodium reduction, weight loss, the Dietary Approach to Stop Hypertension (DASH) diet, and regular aerobic exercise. However, no trial has assessed the efficacy of simultaneously implementing all of these recommendations. The objective of this study was to determine the effects on blood pressure and other cardiovascular disease risk factors of a comprehensive lifestyle intervention. We conducted a randomized controlled trial of 44 hypertensive, overweight adults on a single blood pressure medication. Participants were randomized to a lifestyle or control group. For 9 weeks, the lifestyle group was fed a hypocaloric version of the DASH diet that provided 100 mmol/d of sodium. This group also participated in a supervised, moderate-intensity exercise program 3 times per week. The control group received no intervention. Outcomes were ambulatory blood pressure, serum lipids, weight, and fitness. At the end of the intervention, mean weight loss in the lifestyle group, net of control, was 4.9 kilograms. In the lifestyle group mean net reductions in 24-hour ambulatory systolic and diastolic blood pressures were 9.5 mm Hg (P<0.001) and 5.3 mm Hg (P<0.002), respectively. Corresponding changes in daytime systolic and diastolic blood pressures were 12.1 mm Hg (P<0.001) and 6.6 mm Hg (P<0.001). The lifestyle group experienced mean reductions in total cholesterol (−25 mg/dL,P<0.001), low-density lipoprotein cholesterol (−18 mg/dL,P=0.005), high-density lipoprotein cholesterol (−5 mg/dL,P<0.001), net of control. In conclusion, among hypertensive overweight adults already on antihypertensive medication, a comprehensive lifestyle intervention can substantially lower blood pressure and improve blood pressure control.