High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-individual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08-1.70]; P=0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04-2.33]; P=0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07-2.79]; P=0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04-1.54]; P=0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for individuals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously. Registration- URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01038583; URL: https://www.isrctn.com; Unique identifiers: ISRCTN83772183.