Background: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of heart failure with reduced ejection fraction (HFrEF). Aims: (1) To describe and compare the clinical characteristics and the use of diagnostic and therapeutic procedures among subjects hospitalized with HFrEF according to the presence of type 2 diabetes mellitus (T2DM) and sex; (2) to assess the effect of T2DM and sex on hospital outcomes among the patients hospitalized with HFrEF using propensity score matching (PSM); and (3) to identify which clinical variables were associated to in-hospital mortality (IHM) among the patients hospitalized with HFrEF and T2DM according to their sex. Methods: A retrospective cohort study from 2016 to 2019 using the Spanish National Hospital Discharge Database was conducted. The diagnosis and procedures were codified with the International Classification of Disease 10th version (ICD10). Subjects aged ≥ 40 with a primary diagnosis of HFrEF were included. We included those patients with a diagnosis of T2DM in any diagnosis position. The descriptive statistics used were total and relative frequencies (percentages), means with standard deviations, and medians with an interquartile range. To control the effect of confounding variables when T2DM patients and non-T2DM patients were compared, we matched the cohorts using PSM. Multivariable logistic regression models were used to identify which study variables independently affected the IHM among men and women with HF and T2DM. Also, this multivariable method was applied for sensitivity analyses to confirm the results of the PSM. Results: A total of 28,894 patients were included. T2DM was present in 39.59%. Women with T2DM more frequently had atrial fibrillation, valvular heart disease, anemia, dementia, depression, and hyponatremia than men with T2DM. However, men had more coronary heart disease, chronic renal disease, COPD, and obstructive sleep apnea. All the procedures were significantly more commonly used among men than women. Blood transfusion was the only procedure more frequently identified among women with T2DM. For the sensitivity analysis in patients with T2DM hospitalized with HFrEF, we confirmed the results of the PSM, finding that women had a 14% higher risk of dying in the hospital than men (OR 1.14; 95% CI 1.01–1.35). Obesity seemed to have a protective effect (OR 0.85; 95% CI 0.73–0.98) on the in-hospital morality. Conclusions: Subjects with diabetes are admitted for HFrEF and have a greater number of comorbidities than non-diabetics. Diabetic women have a higher mortality rate than men with diabetes and all the procedures evaluated were significantly more often used among men than women.