Heart failure with preserved ejection fraction (HFpEF) affects more women than men, suggesting gender to play a major role in disease evolution. However, studies investigating gender differences in HFpEF are limited. In the present study we aimed to describe gender differences in a well-characterized HFpEF cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment, cardiac magnetic resonance imaging and exercise testing. Study endpoints were: cardiac death, a combined endpoint of HF hospitalization or cardiac death and all-cause death. 260 HFpEF patients were prospectively enrolled. Men were more compromised with regard to exercise capacity and had significantly more co-morbidities. Men had more pronounced pulmonary vascular disease with higher diastolic pressure gradients and a lower right ventricular EF. During follow-up, 9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause death. Male gender was independently associated with cardiac death, but neither with the combined endpoint nor with all-cause mortality. We detected clear gender differences in HFpEF patients. Cardiac death was more common among men, but not all-cause death. While men are more prone to develop a right heart phenotype and die from HFpEF, women are more likely to die with HFpEF.