Abstract Background/Introduction Isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension (CH) are related with increased cardiovascular risk. Purpose The aim of the present study was to compare the predictive role of ISH and CH for the incidence of atrial fibrillation (AF) in a cohort of essential hypertensive patients. Methods We followed up 1605 essential hypertensives with office systolic blood pressure (BP)≥140 mmHg [mean age 58.1 years, 842 males, office BP=153/92 mmHg] for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent echocardiographic study and blood sampling for estimation of metabolic profile. Patients with baseline ISH exhibited office systolic BP ≥140 mmHg and office diastolic BP <90 mmHg, while those with CH had office systolic BP ≥140 mmHg and office diastolic BP ≥90 mmHg. Moreover, new-onset AF was defined as hospitalization for AF or compatible electrocardiographic tracings. Results The incidence of new-onset AF over the follow-up period was 3.4% (n=55). Patients with ISH (n=510) compared to those with CH (n=1095) were older (65±10 vs 55±11 years, p<0.0001), had at baseline lower waist circumference (95.5±12 vs 98±12 cm, p<0.0001), office systolic BP (149±10 vs 155±13 mmHg, p<0.0001), office diastolic BP (80±5 vs 98±7 mmHg, p<0.0001), while did not differ regarding left ventricular mass index and lipid levels (p=NS for all). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio=4.612, p=0.013) and CH (hazard ratio=1.794, p=0.036) predicted new-onset AF. However, in multivariate Cox regression model, age (hazard ratio=1.078, p<0.001), left ventricular mass index (hazard ratio 1.012, p=0.014), left atrium diameter (hazard ratio=1.102, p<0.001) and ISH (hazard ratio=1.551, p=0.035) but not CH turned out to be independent predictors of new-onset AF episodes. Conclusions In essential hypertensive patients, ISH but not CH exhibits independent prognostic value for AF. These findings support that ISH constitutes a hypertensive phenotype of particularly increased arrhythmia risk needing careful evaluation and treatment.