Objective: Blood pressure (BP) variability is the physiological sequelae of the complex interaction of multiple neural, humoral, reflex, and behavioral factors. This analysis aimed to evaluate the determinants of BP variability and instability within a single office visit, which is routinely used for hypertension evaluation in clinical practice. Design and method: A retrospective analysis of cross-sectional data was performed, comprising adults with triplicate office BP measurements in a single office visit and 24h ambulatory BP monitoring collected within the context of prospective clinical studies in Finland, Greece, and United Kingdom. Indices of BP variability and instability included: (i) standard deviation (SD) (ii) coefficient of variation (CV) (iii) average real variability (ARV) (iv) maximum office BP (Max) (v) maximum-minimum difference (MMD) of office BP (vi) ratio of the difference between 1st-3rd measurement to the mean office BP (Relative change). White-coat effect was defined as the difference between office and daytime ambulatory BP. Results: Data from 1.053 individuals were analyzed (mean age 57.7 ± 11.3 years, males 50%, treated hypertensives 50.3%, average office BP 133.5 ± 18.7/83.5 ± 10.9 mmHg, daytime ambulatory BP 132.5 ± 14.1/80.7 ± 9.9 mmHg). All the indices of BP variability and instability were positively associated with average office BP, age, BMI, and white-coat effect, but with an inverse association between age and maximum diastolic BP (all p < 0.05). In multivariable linear regression analysis systolic BP variability was mainly determined by average office systolic BP, and treatment for hypertension, while diastolic BP variability was determined by office diastolic BP and female sex (Table). Conclusions: These results suggest that the variability and instability of BP within a single office visit is mainly influenced by the BP level, female sex and the administration of antihypertensive treatment.