Blood pressure (BP) is known to vary by time of day and day of year. Studies differ substantially on the magnitude of the effect and there is doubt whether variation is clinically meaningful. We used more than 2 million BP measurements obtained between 1996 and 2004 from Geisinger Clinic primary care patients. General estimating equations were used to determine the effect of time of day and month of year on the probability of identifying BP values above four diagnostic cutoff points (SBP > or =120 mm Hg, SBP > or =140 mm Hg, DBP > or =80 mm Hg, DBP > or =90 mm Hg). Time of day and month of year were significantly associated with the odds of measuring elevated BP, regardless of definition. The odds ratio (OR) for SBP > or =120 mm Hg in the evening (1900 hours) versus midday (1200 hours) was 1.32 (P < 0.001). The OR for SBP > or =120 mm Hg in winter to summer months was 1.24 (P < 0.001). Similar results were found for each age/gender group. These data indicate that in clinical practice, measurement of an elevated BP may vary by 40% depending on the time of day and month of year. The magnitude of the variability in BP measurement attributable to the combined effect of these temporal factors is clinically significant. Anticipation of changes in BP attributable to temporal factors may improve accuracy of diagnosis and precision of therapy.