Little is known on how frailty influences clinical outcomes in persons with specific multimorbidity patterns.To investigate the interplay between multimorbidity and frailty in the association with mortality in older individuals living in nursing homes (NH).We considered 4,131 NH residents aged 60 years and over, assessed through the interRAI LTCF instrument between 2014 and 2018. Follow-up was until 2019. Considering four multimorbidity patterns identified via principal component analysis, subjects were stratified in tertiles (T) with respect to their loading values. Frailty Index (FI) considered 23 variables and a cut-off of 0.24 distinguished between high and low frailty levels. For each pattern, all possible combinations of tertiles and FI were evaluated. Their association (Hazard Ratio [HR] and 95% confidence interval) with mortality was tested in Cox regression models.In the heart diseases and dementia and sensory impairments patterns, the hazard of death increases progressively with patterns expression and frailty severity (being HR T3 vs. T1 = 2.36 [2.01-2.78]; HR T3 vs. T1 = 2.12 [1.83-2.47], respectively). In heart, respiratory and psychiatric diseases and diabetes, musculoskeletal and vascular diseases patterns, frailty seems to have a stronger impact on mortality than patterns' expression.Frailty increases mortality risk in all the patterns and provides additional prognostic information in NH residents with different multimorbidity patterns.These findings support the need to routinely assess frailty. Older people affected by specific groups of chronic diseases need a specific care approach and have high risk of negative health outcomes.