https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e2.htm?s_cid=mm7017e2_w **Summary** _**What is already known about this topic?**_ COVID-19 vaccines have demonstrated high efficacy in clinical trials. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. _**What is added by this report?**_ In a COVID-19 outbreak at a Kentucky SNF involving a newly introduced variant to the region, unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of infection as did vaccinated residents and HCP. Vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among HCP. _**What are the implications for public health practice?**_ Vaccination of SNF residents and HCP is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices. _COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021_ _Weekly / April 30, 2021 / 70(17);639-643_ _On April 21, 2021, this report was posted online as an MMWR Early Release._