Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. We performed 24-h ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mmHg), normal (130/85 mmHg), and high (140/90 mmHg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 118.3/74.2 mmHg for 24 h, 121.6/78.9 mmHg for daytime, and 104.7/65.3 mmHg for nighttime. Corresponding thresholds for normal ABP were 124.3/76.8, 129.9/82.6, and 111.6/68.1 mmHg, respectively, and those for ambulatory hypertension were 130.3/79.4, 138.2/86.4, and 118.5/70.8 mmHg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mmHg for 24 h, 120/80 mmHg for daytime, and 105/65 mmHg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mmHg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mmHg. In conclusion, population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.