Stress-reactivity has long been proposed to act as a possible mechanism linking psychological factors and increases in blood pressure (BP). This study used results from an intensive cardiovascular investigation to examine the mediating role of reactivity in the relationship between defensiveness and 3-year ambulatory BP levels. A total of 125 male and female participants (M = 29.1 years) completed a protocol including laboratory reactivity testing, 8- to 12-hr ambulatory BP monitoring, and standardized response style instruments. Further, participants returned 3 years later for an identical second test protocol. Results indicated that high- and low-defensiveness participants did not differ on Year 1 BP, but the high-defensiveness group showed higher BP during the reactivity tasks and on Year 3 ambulatory measures. Statistical mediation testing supported reactivity levels as an intervening mechanism between defensiveness and 3-year BP levels.