Background Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from population-based studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care. Methods We analyzed data from a registry-based, multicenter, national cohort that included 63,910 adults recruited from 2004 through 2014 in Spain. Clinic and 24-hour ambulatory blood-pressure data were examined in the following categories: sustained hypertension (elevated clinic and elevated 24-hour ambulatory blood pressure), "white-coat" hypertension (elevated clinic and normal 24-hour ambulatory blood pressure), masked hypertension (normal clinic and elevated 24-hour ambulatory blood pressure), and normotension (normal clinic and normal 24-hour ambulatory blood pressure). Analyses were conducted with Cox regression models, adjusted for clinic and 24-hour ambulatory blood pressures and for confounders. Results During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. In a model that included both 24-hour and clinic measurements, 24-hour systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% confidence interval [CI], 1.56 to 1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure (hazard ratio, 1.02; 95% CI, 1.00 to 1.04, after adjustment for 24-hour blood pressure). Corresponding hazard ratios per 1-SD increase in pressure were 1.55 (95% CI, 1.53 to 1.57, after adjustment for clinic and daytime blood pressures) for nighttime ambulatory systolic pressure and 1.54 (95% CI, 1.52 to 1.56, after adjustment for clinic and nighttime blood pressures) for daytime ambulatory systolic pressure. These relationships were consistent across subgroups of age, sex, and status with respect to obesity, diabetes, cardiovascular disease, and antihypertensive treatment. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12 to 3.79) than sustained hypertension (hazard ratio, 1.80; 95% CI, 1.41 to 2.31) or white-coat hypertension (hazard ratio, 1.79; 95% CI, 1.38 to 2.32). Results for cardiovascular mortality were similar to those for all-cause mortality. Conclusions Ambulatory blood-pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. White-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension. (Funded by the Spanish Society of Hypertension and others.)