BACKGROUND: The prognostic relevance of a hypertensive response to exercise (HRE) is ill-defined in individuals undergoing exercise stress testing. The study described here was intended to provide a systematic review and meta-analysis of published literature to determine the value of exercise-related blood pressure (BP) (independent of office BP) for predicting cardiovascular (CV) events and mortality. METHODS: Online databases were searched for published longitudinal studies reporting exercise-related BP and CV events and mortality rates. RESULTS: We identified for review 12 longitudinal studies with a total of 46,314 individuals without significant coronary artery disease, with total CV event and mortality rates recorded over a mean follow-up of 15.2±4.0 years. After adjustment for age, office BP, and CV risk factors, an HRE at moderate exercise intensity carried a 36% greater rate of CV events and mortality (95% CI, 1.02-1.83, P = 0.039) than that of subjects without an HRE. Additionally, each 10mm Hg increase in systolic BP during exercise at moderate intensity was accompanied by a 4% increase in CV events and mortality, independent of office BP, age, or CV risk factors (95% CI, 1.01-1.07, P = 0.02). Systolic BP at maximal workload was not significantly associated with the outcome of an increased rate of CV, whether analyzed as a categorical (HR=1.49, 95% CI, 0.90-2.46, P = 0.12) or a continuous (HR=1.01, 95% CI, 0.98-1.04, P = 0.53) variable. CONCLUSIONS: An HRE at moderate exercise intensity during exercise stress testing is an independent risk factor for CV events and mortality. This highlights the need to determine underlying pathophysiological mechanisms of exercise-induced hypertension.