Objective: The aim was to examine the effects of a Mindfulness-Based Stress Reduction (MBSR) intervention on cardiovascular and cortisol activity during acute stress. Method: Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were randomly assigned to the MBSR protocol or a waitlist control group. Before and after the intervention period they participated in a laboratory stress protocol consisting of mental arithmetic and speech tasks. Laboratory measurements included continuous cardiovascular parameters (heart period, heart rate variability, and systolic and diastolic blood pressure [SBP and DBP]), and salivary cortisol. Results: Compared to the control group and controlling for age, sex, body mass index, and beta-blockers, the MBSR group showed larger pre- to postintervention decreases in overall SBP (F(1, 58) =4.99, p = .029, partial eta(2) = .08) and DBP (F(1, 58) = 11.09, p = .002, partial eta(2) = .16). In addition, the MBSR group exhibited smaller SBP and DBP stress-related changes from pre- to postintervention (F(2, 116) =4.89, p = .012, partial eta(2) = .08; F(2, 116) = 6.07, p = .007, partial eta(2) = .10, respectively). No effects were obtained on other physiological measures. Conculsion: MBSR may help reducing blood pressure levels and blood pressure reactivity to stress.