INTRODUCTION: Naturalistic studies are essential to prospectively study real-world antihypertensive treatment OBJECTIVE: to evaluate the feasibility of performing a naturalistic study in newly diagnosed hypertensives in terms of enrollment, adequacy, timeliness of data collection, and study procedures. METHODS: CHOICE prospectively collected actual practice data on the treatment of newly-diagnosed hypertensive patients. Initial therapy was randomly assigned to either Group 1 (beta blockers or diuretics) or Group 2 (ACE inhibitors or calcium channel blockers). The protocol made no demands in scheduling visits or changing treatment during follow-up. Physicians were blind to study purpose and hypotheses. Only a final visit at 5±1 months, if none occurred naturally, was mandated. Direct involvement of the CHOICE study team was minimized using a Remote Study Monitoring System to collect data and communicate with study sites. RESULTS: Within 30 weeks, a total of 55 physicians enrolled 512 patients with a mean age of 51 years and blood pressure of 158/99 mmHG. In all, 46 different antihypertensive medications were prescribed and 2,554 office visits (range=1-16 visits per patient) were attended. Other medical resource use was low during the study period. A final, clean database was ready for analysis 30 days after last patient last visit. CONCLUSIONS: It has been demonstrated that CHOICE is a feasible framework to study the real-world effectiveness of initial therapy for newly diagnosed hypertension. Protocol flexibility and a novel electronic data entry system are core elements of this naturalistic design.