Introduction: Heart failure decompensation can be triggered by many factors, including anemia. In cases of iron deficiency anemia or iron deficiency without anemia, endoscopic studies are recommended to rule out the presence of gastrointestinal neoplasms or other associated bleeding lesions. Objectives: The aims of this study were to (i) examine trends in the incidence, clinical characteristics, and in-hospital outcomes of patients hospitalized with heart failure from 2002 to 2017 who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy, and to (ii) identify factors associated with in-hospital mortality (IHM) among patients with heart failure who underwent an EGD and/or a colonoscopy. Methods: We conducted an observational retrospective epidemiological study using the Spanish National Hospital Discharge Database (SNHDD) between 2002 and 2017. We included hospitalizations of patients with a primary discharge diagnosis of heart failure. Cases were reviewed if there was an ICD-9-CM or ICD-10 procedure code for EGD or colonoscopy in any procedure field. Multivariable logistic regression models were constructed to identify predictors of IHM among HF patients who underwent an EGD or colonoscopy. Results: A total of 51,187 (1.32%) non-surgical patients hospitalized with heart failure underwent an EGD and another 72,076 (1.85%) patients had a colonoscopy during their admission. IHM was significantly higher in those who underwent an EGD than in those who underwent a red blood cell transfusion (OR 1.10; 95%CI 1.04–1.12). However, the use of colonoscopy seems to decrease the probability of IHM (OR 0.45; 95%CI 0.41–0.49). In patients who underwent a colonoscopy, older age seems to increase the probability of IHM. However, EGD was associated with a lower mortality (OR 0.60; 95% CI 0.55–0.64). Conclusion: In our study, a decrease in the number of gastroscopies was observed in relation to colonoscopy in patients with heart failure. The significant ageing of the hospitalized HF population seen over the course of the study could have contributed to this. Both procedures seemed to be associated with lower in-hospital mortality, but in the case of colonoscopy, the risk of in-hospital mortality was higher in elderly patients with heart failure and associated neoplasms. Colonoscopy and EGD seemed not to increase IHM in patients with heart failure.