Background: In patients with heart failure with preserved ejection fraction (HFpEF), worse kidney function is associated with worse overall cardiac mechanics. Right ventricular stroke work index (RVSWI) is a parameter of right ventricular function. The aim of our study was to determine the relationship between RVSWI and glomerular filtration rate (GFR) in patients with HFpEF. Method: This was a single-center cross-sectional study. HFpEF is defined as patients with documented heart failure with ejection fraction > 50% and pulmonary wedge pressure > 15 mm Hg from right heart catheterization. RVSWI (normal value 8–12 g/m/beat/m2) was calculated using the formula: RVSWI = 0.0136 × stroke volume index × (mean pulmonary artery pressure – mean right atrial pressure). Univariate and multivariate linear regression analysis was performed to study the correlation between RVSWI and GFR. Result: Ninety-one patients were included in the study. The patients were predominantly female (n = 64, 70%) and African American (n = 61, 67%). Mean age was 66 ± 12 years. Mean GFR was 59 ± 35 mL/min/1.73 m2. Mean RVSWI was 11 ± 6 g/m/beat/m2. Linear regression analysis showed that there was a significant independent inverse relationship between RVSWI and GFR (unstandardized coefficient = –1.3, p = 0.029). In the subgroup with combined post and precapillary pulmonary hypertension (Cpc-PH) the association remained significant (unstandardized coefficient = –1.74, 95% CI –3.37 to –0.11, p = 0.04). Conclusion: High right ventricular workload indicated by high RVSWI is associated with worse renal function in patients with Cpc-PH. Further prospective studies are needed to better understand this association.