OBJECTIVES: The clinical significance of isolated systolic hypertension (ISH) in the young is still controversial. Aim of the present study was to investigate whether prognosis of ISH in young-to-middle-age individuals differs according to central blood pressure (BP). DESIGN: We studied 354 participants screened for stage 1 hypertension and 34 normotensive controls to determine which individuals developed hypertension needing drug therapy. Among the hypertensive patients, 67 had ISH and were divided according to whether their central SBP, measured with applanation tonometry, was above (ISH-high) or below (ISH-low) the median (120.5 mmHg). Large artery (C1) and small artery (C2) compliance were also measured. RESULTS: Compared to normotensive individuals, ISH-high had decreased C1 (P = 0.02) and C2 (P = 0.01), and higher peripheral resistance (P = 0.01). In contrast, in ISH-low, all these variables were similar to those in normotensive individuals. During 9.5 years of follow-up, incident hypertension was more common among participants with systolic-diastolic hypertension (SDH) and ISH-high than the other two groups [odds ratio (OR) = 6.2, 95% confidence interval (CI) = 1.8-21.1, P = 0.003 for SDH; OR = 6.0, 95% CI = 1.5-24.0, P = 0.01 for ISH-high, versus normotensive individuals]. Among ISH-low, incidence of hypertension was only slightly higher than that in normotensive individuals (OR = 1.1, 95% CI 0.2-5.3, P = 0.90) and lower than that in ISH-high (P = 0.03). These associations remained significant when ambulatory BP was included in the models or when the 125 mmHg cut-off for central BP was used to identify ISH subgroups. CONCLUSION: These data show that young-to-middle-age ISH individuals with low central BP have a lower risk of hypertension needing treatment than those with high central BP. These results are applicable mainly to male individuals.