Background: Most healthy people exhibit a decrease in systolic blood pressure (SBP) at night. A drop of <10% from mean daytime values, "non-dipping," is associated with kidney disease and cardiovascular events. We hypothesized that non-dipping would predict all-cause mortality. Methods: Consecutive patients referred for ambulatory blood pressure (BP) monitoring at the Cleveland Clinic between 1994 and 2004 were included. Mean daytime (6 AM-11 PM) and nighttime (11 PM-6 AM) SBP values were calculated. We examined diurnal BP variation as a continuous variable, ((Mean daytime SBP - Mean nighttime SBP)/(Mean daytime SBP)) × 100%, and also as a categorical variable, defining "non-dipping" as a nocturnal SBP drop of <10%; subjects who exhibited non-dipping were defined as "non-dippers" and the others as "dippers." All-cause mortality was ascertained from the Social Security Death Index. Results: Of the 621 patients included in the study, 261 were dippers and 360 were non-dippers. Non-dippers were older (P < 0.0001), more likely to be non-white (P < 0.05), and had higher rates of smoking, diabetes, hypertension, coronary artery disease, congestive heart failure, and renal insufficiency (P < 0.01 for all). Over a mean follow-up of 6.3 years, 61 patients died, including 10 dippers (3.8%) and 51 non-dippers (14.2%). The unadjusted hazard ratio for death based upon a decrement in the dipping percentage from the 75th to 25th percentile was 2.22 (95% confidence interval 1.64-2.95; P < 0.0001). This was attenuated after adjustment for comorbid conditions, including mean 24-h SBP and renal function: adjusted hazard ratio 1.62 (1.14-2.24; P < 0.005). Conclusions: Blunted diurnal BP variation is a strong predictor of death, but this may be accounted for, in large part, by its association with other cardiovascular risk factors.