Background: Neutropenic fever (NF) remains one of the most common causes for hospitalization and mortality in oncology patients. Concomitant cardiovascular disease in patients with cancer is not uncommon. There is limited data on the impact of cardiovascular (CVS) comorbidities on mortality in cancer patients with NF. Methods: This is a retrospective cohort study using the 2016 National Inpatient Sample database (NIS) of adults ( > 18 years) admitted for NF based on the ICD-10 code. Mortality was the primary outcome. Multivariate linear regression adjusted for potential confounder of age, sex, race, Charlson comorbidity index and all the CVS comorbidities of the study including atrial fibrillation (AF), heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), coronary artery disease (CAD), peripheral vascular disease (PVD), hypertension (HTN), history of smoking, history of cerebrovascular accident (CVA) or TIA and dyslipidemia. STATA 15 was used for analysis. Results: We identified 31,310 patients (mean age 44.6) (49.6% females) admitted with NF, among which 250 died during same admission. On multivariate linear regression there was a significant increase in adjusted all-cause mortality in patients with AF (OR: 2.39; 95%-CI 1.06- 5.40, P = 0.035) and HFpEF (OR: 4.30; 95%-CI 1.08- 17.17, P = 0.039). There was no significant increase in mortality in patients with HFrEF, dyslipidemia, HTN, PVD, CAD, history of CVA/TIA and smoking. Conclusions: Patients with NF and concomitant history of AF or HFpEF have an increased risk of mortality during hospitalization. Inflammation is emerging as a key player in AF pathogenesis. This may explain why AF appears to correlate with mortality, as those with more severe presentations are more likely to have a heightened state of inflammation. Patients with NF are more likely to receive fluids in the setting of infectious complications which could explain the increased mortality in CHF patients with NF. Identifying risk factors for increased mortality in patients with NF is important for risk stratification and in guiding clinicians in the management of this delicate population.