The role of pulse pressure in young individuals remains controversial. The aim of the present study was to investigate the clinical significance of elevated pulse pressure in young- to middle-aged subjects screened for stage 1 hypertension. We examined 1241 subjects (mean age, 33.1±8.4 years) from the HARVEST (Hypertension Ambulatory Recording Venetia Study), during a median follow-up of 12.1 years. To evaluate the predictive value of pulse pressure and mean blood pressure for future hypertension needing treatment and for cardiovascular events, participants were grouped into pressure tertiles. Significant determinants of pulse pressure were male sex (P=0.029), younger age (P<0.001), physical activity (P=0.003), heart rate (P<0.001), systolic white-coat effect (P<0.001), and stroke volume (n=829; P<0.001). During follow-up, 65.1% of participants developed hypertension requiring pharmacological treatment and 5.1% experienced a cardiovascular event. Participants in the highest pulse pressure tertile had a reduced risk of incident hypertension compared with those of the bottom tertile (hazard ratio, 0.75; 95% confidence interval, 0.62–0.91; P=0.003). In contrast, participants in the top mean blood pressure tertile had an increase in risk (1.91; 1.57–2.33; P<0.001). In addition, participants in the highest pulse pressure tertile had a reduced risk of cardiovascular events (0.35; 0.17–0.73; P=0.005) and those in the top mean blood pressure tertile had an increase in risk (3.06; 1.32–7.09; P=0.009). Our data show that in subjects <45 years, only mean blood pressure is a predictor of adverse outcome whereas high pulse pressure even carries a reduced risk.