Identifying effective, nonpharmacologic means of preventing or significantly delaying the onset of hypertension would be a major advance in the primary prevention of cardiovascular disease. In the first phase of the Trials of Hypertension Prevention (TOHP I), adults with high-normal diastolic blood pressure were randomly assigned to one of seven nonpharmacologic interventions. Only weight loss and reduction of dietary sodium proved to be effective strategies for reducing blood pressure. The second phase of TOHP (TOHP II) will test the effectiveness of weight loss, reduction of dietary sodium, and their combination of lowering blood pressure and preventing the onset of hypertension over a 3- to 4-year follow-up period. This article describes the three interventions used in TOHP II, methods used to maintain continued participation in this long-term trial, and protocol enhancements designed to maximize intervention effectiveness.