Dementia is associated with high rates of admission to hospital, due to acute illness, and in-hospital mortality. The study aimed to investigate the impact of dementia on in-hospital mortality and identify the predictors of in-hospital mortality in these patients. This was a retrospective study evaluating all the patients ≥65 years consecutively admitted to our Emergency Department (ED). We compared the clinical outcomes of the patients with dementia at ED admission with those who did not have dementia, using a propensity score-matched (PSM) paired cohort of controls. The patients were matched for age, sex, Charlson Comorbidity Index value, and clinical severity at presentation (based on NEWS ≥ 5). The primary study endpoint was all-cause in-hospital death. After the PSM, a total of 7118 patients, 3559 with dementia and 3559 in the control group, were included in the study cohort. The mean age was 84 years, and 59.8% were females. The overall mortality rate was higher for the demented patients compared with the controls (18.7% vs. 16.0%, = 0.002). The multivariate-adjusted hazard ratio (HR) showed that dementia was an independent risk factor for death (HR 1.13 [1.01-1.27]; = 0.033). In the patients with dementia, respiratory failure (HR 3.08 [2.6-3.65]), acute renal failure (HR 1.64 [1.33-2.02]; < 0.001), hemorrhagic stroke (HR 1.84 [1.38-2.44]; < 0.001), and bloodstream infection (HR 1.41 [1.17-1.71]; = 0.001) were significant predictors of worse outcomes. Finally, the comorbidities and severity of illness at ED admission negatively influenced survival among the patients with dementia (CCI HR 1.05 [1.01-1.1] = 0.005; NEWS ≥ 5 HR 2.45 [1.88-3.2] < 0.001). In conclusion, among the hospitalized older patients, dementia was associated with a higher risk of mortality. Furthermore, among the older patients with dementia, respiratory failure and bloodstream infections were independently associated with an increased risk of in-hospital mortality.