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Background Nursing homes are highly vulnerable to the occurrence of COVID-19 outbreaks, which result in high lethality rates. Most of them are not prepared to SARS-CoV-2 pandemic. Methods A coordinated on-site medicalization program (MP) in response to a sizeable COVID-19 outbreak in four nursing homes was organized, with the objectives of improving survival, offering humanistic palliative care to residents in their natural environment, and reducing hospital referrals. Ten key processes and interventions were established (provision of informatics infrastructure, medical equipment, and human resources, universal testing, separation of 'clean' and 'contaminated' areas, epidemiological surveys, and unified protocols stratifying for active or palliative care approach, among others). Main outcomes were a composite endpoint of survival or optimal palliative care (SOPC), survival, and referral to hospital. Results 272 out of 457 (59.5%) residents and 85 out of 320 (26.5%) staff members were affected. The SOPC, survival, and referrals to hospital, occurred in 77%, 72.5%, and 29% of patients diagnosed before MP start, with respect to 97%, 83.7% and 17% of those diagnosed during the program, respectively. The SOPC was independently associated to MP (OR=15 [3-81]); and survival in patients stratified to active approach, to the use of any antiviral treatment (OR=28 [5-160]). All outbreaks were controlled in 39 [37-42] days. Conclusions A coordinated on-site medicalization program of nursing homes with COVID-19 outbreaks achieved a higher survival or optimal palliative care rate, and a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents.

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