The association between isolated systolic hypertension (ISH) and incident heart failure (HF) has not been prospectively studied in a propensity-matched population of ambulatory older adults. Of the 5795 participants in the public-use copy of the Cardiovascular Health Study data set, 5248 had diastolic blood pressure <90 mm Hg and were free of HF at baseline. Of these, 2000 (38%) had ISH, defined as average seated systolic blood pressure > or =140 mm Hg. Propensity scores for baseline ISH were calculated for each participant (based on 64 baseline covariates) and were used to match 1260 pairs of participants with and without ISH. Matched Cox regression models were used to estimate the association of ISH with incident HF during a mean follow-up of 8.7 years. Matched participants (n=2520) had a mean (+/-SD) age of 74 (+/-6) years, 60% were women, 16% were nonwhites, 18% developed new-onset HF, and 35% died. Incident HF developed in 20% (rate: 242/10,000 person-years) and 16% (rate: 194/10,000 person-years) of participants with and without ISH, respectively (matched hazard ratio when ISH was compared with no ISH: 1.26; 95% CI: 1.04 to 1.51; P=0.016). Prematch unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% CIs) for ISH-associated incident HF were, respectively, 1.72 (1.51 to 1.97; P<0.0001), 1.35 (1.18 to 1.56; P<0.0001), and 1.22 (1.04 to 1.44; P=0.016). ISH had no association with all-cause mortality (matched hazard ratio: 1.03; 95% CI: 0.88 to 1.19; P=0.732). In conclusion, in a propensity-matched cohort of community-dwelling older adults who were well balanced in 64 baseline covariates, ISH was associated with increased risk of incident HF but had no association with all-cause mortality.