AIM: Coronavirus-19 disease (COVID-19) is a widespread condition in nursing home (NH). It is not known whether COVID-19 is associated with a higher risk of death than residents without COVID-19. Therefore, the aim of this study was to assess whether COVID-19 is associated with a higher mortality rate in NH residents, considering frailty status assessed with the Multidimensional Prognostic Index (MPI). METHODS: In this retrospective study, made in 31 NHs in Venice, Italy, the presence of COVID-19 was ascertained with a nasopharyngeal swab. Frailty was evaluated using the MPI, modified according to the tools commonly used in our NHs. A Cox's regression analysis was used reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs), using COVID-19 as exposure and mortality as outcome and stratified by MPI tertiles. Similar analyses were run using MPI tertiles as exposure. RESULTS: Overall, 3946 NH residents (median age = 87 years, females: 73.9%) were eligible, with 1136 COVID-19 + . During a median follow-up of 275 days, higher values of MPI, indicating frailer people, were associated with an increased risk of mortality. The incidence of mortality in COVID-19 + was more than doubled than COVID-19- either in MPI-1, MPI-2 and MPI-3 groups. The presence of COVID-19 increased the risk of death (HR = 1.85; 95% CI 1.59-2.15), also in the propensity score model using MPI as confounder (HR = 2.48; 95% CI 2.10-2.93). CONCLUSION: In this retrospective study of NH residents, COVID-19 was associated with a higher risk of all-cause mortality than those not affected by COVID-19 also considering the different grades of frailty.