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The aim was to characterize multimorbidity patterns in a large sample of older individuals living in nursing homes (NHs) and to investigate their association with mortality, also considering the effect of functional status. Observational and retrospective study. We analyzed data on 4131 NH residents in Italy, aged 60 years and older, assessed through the interRAI long-term care facility instrument. Entry date was between 2014 and 2018, and participants were followed until 2019. Multimorbidity patterns were identified through principal component analysis; for the identified components, subjects were stratified in quintiles (Q) with respect to their loading values, with the higher quantiles indicating greater expression of the component's pattern. Their association [hazard ratio (HR) and 95% CI] with mortality was tested in Cox regression models. Analyses were stratified by disability status. Four patterns of multimorbidity were identified: (1) heart diseases ; (2) dementia and sensory impairments ; (3) heart, respiratory, and psychiatric diseases; and (4) diabetes, musculoskeletal, and vascular diseases. For the heart diseases pattern [HR Q5 vs Q1 = 1.83 (1.53–2.20)] and the dementia and sensory impairments pattern [HR Q5 vs Q1 = 1.23 (1.06–1.42)], as the specific multimorbidity expression increases, the risk of mortality increases. On stratifying by disability status, the association between the multimorbidity patterns and mortality was not always present. Different multimorbidity patterns are differentially associated with mortality in older residents of NHs, confirming that multimorbidity's prognosis is strictly dependent on the underlying disease combinations. This knowledge may be useful to implement personalized preventive and therapeutic care pathways for institutionalized older adults, which respond to individuals' health needs. [ABSTRACT FROM AUTHOR]