The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary study was to evaluate the effect of intensive versus standard clinic-based BP targets on ambulatory BP. Ambulatory BP was obtained within 3 weeks of the 27-month study visit in 897 SPRINT participants. Intensive treatment resulted in lower clinic systolic BP (mean difference between groups=16.0 mm Hg; 95% confidence interval, 14.1-17.8 mm Hg), nighttime systolic BP (mean difference=9.6 mm Hg; 95% confidence interval, 7.7-11.5 mm Hg), daytime systolic BP (mean difference=12.3 mm Hg; 95% confidence interval, 10.6-13.9 mm Hg), and 24-hour systolic BP (mean difference=11.2 mm Hg; 95% confidence interval, 9.7-12.8 mm Hg). The night/day systolic BP ratio was similar between the intensive (0.92±0.09) and standard-treatment groups (0.91±0.09). There was considerable lack of agreement within participants between clinic systolic BP and daytime ambulatory systolic BP with wide limits of agreement on Bland-Altman plots. In conclusion, targeting a systolic BP of <120 mm Hg, when compared with <140 mm Hg, resulted in lower nighttime, daytime, and 24-hour systolic BP, but did not change the night/day systolic BP ratio. Ambulatory BP monitoring may be required to assess the effect of targeted hypertension therapy on out of office BP. Further studies are needed to assess whether targeting hypertension therapy based on ambulatory BP improves clinical outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835249.