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Purpose: Identifying mortality risk factors in people living in nursing homes could help healthcare professionals to individualize or develop specific plans for predicting future care demands and plan end-of-life care in this population. This study aims to identify mortality risk factors in elderly nursing home (NH) residents, based on variables adapted to this environment, routinely collected and easily accessible to their healthcare professionals. Methods: A prospective, longitudinal, observational study of NH residents aged 65 years and older was carried out collecting sociodemographic, functional and cognitive status, nutritional variables, comorbidities, and other health variables. These variables were analyzed as mortality risk factors by Cox proportional hazard models. Results: A total of 531 residents (75.3% female; average age 86.7 years (SD: 6.6)) were included: 25.6% had total dependence, 53.4% had moderate to severe cognitive impairment, 84.5% were malnourished or at risk of malnutrition, and 79.9% were polymedicated. Risk of mortality (hazard ratio, HR) increased in totally dependent residents (HR = 1.52; p = 0.02) and in those with moderate or severe cognitive impairment ((HR = 1.59; p = 0.031) and (HR = 1.93; p = 0.002), respectively). Male gender (HR = 1.88; p < 0.001), age ≥80 years (HR = 1.73; p = 0.034), hypertension (HR = 1.53; p = 0.012), atrial fibrillation/arrhythmia (HR = 1.43; p = 0.048), and previous record of pneumonia (HR = 1.65; p = 0.029) were also found to be mortality drivers. Conclusion: Age and male gender (due to the higher prevalence of associated comorbidity in these two variables), certain comorbidities (hypertension, atrial fibrillation/arrhythmia, and pneumonia), higher functional and cognitive impairment, and frequency of medical emergency service care increased the risk of mortality in our study. Given their importance and their easy identification by healthcare professionals in nursing homes, these clinical variables should be used for planning care in institutionalized older adults.