This study investigates age-related shifts in the relative importance of systolic (SBP) and diastolic (DBP) blood pressures as predictors of stroke and whether these relations are influenced by other cardiovascular risk factors. Using 34 European cohorts from the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) Project with baseline between 1982 and 1997, 68 551 subjects aged 19 to 78 years, without cardiovascular disease and not receiving antihypertensive treatment, were included. During a mean of 13.2 years of follow-up, stroke incidence was 2.8%. Stroke risk was analyzed using hazard ratios per 10-mm Hg/5-mm Hg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP and DBP simultaneously. Because of nonlinearity, DBP was analyzed separately for DBP ≥ 71 mm Hg and DBP <71 mm Hg. Stroke risk was associated positively with SBP and DBP ≥ 71 mm Hg (SBP/DBP ≥ 71 mm Hg; hazard ratios: 1.15/1.06 [95% CI: 1.12-1.18/1.03-1.09]) and negatively with DBP <71 mm Hg (0.88[0.79-0.98]). The hazard ratio for DBP decreased with age (P<0.001) and was not influenced by other cardiovascular risk factors. Taking into account the age × DBP interaction, both SBP and DBP ≥ 71 mm Hg were significantly associated with stroke risk until age 62 years, but in subjects older than 46 years the superiority of SBP for stroke risk exceeded that of DBP ≥ 71 mm Hg and remained significant until age 78 years. DBP <71 mm Hg became significant at age 50 years with an inverse relation to stroke risk. In Europeans, stroke risk should be assessed by both SBP and DBP until age 62 years with increased focus on SBP from age 47 years. From age 62 years, emphasis should be on SBP without neglecting the potential harm of very low DBP.