A MERS-CoV outbreak occurred at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, from March 29 to May 21, 2014, involving 45 patients, including 8 with external infections, 13 long-term patients, 23 healthcare workers (HCWs), and 1 with an indeterminate source. Molecular epidemiology showed that the outbreak was part of a larger outbreak in Riyadh, likely originating from a single zoonotic transmission event in December 2013. This indicated ongoing healthcare-associated transmission for 5 months. The study used genetic data to trace transmission chains and identify multiple external introductions, supporting or refuting suspected transmission pathways. MERS-CoV was first identified in 2012, with over 1,300 confirmed cases and 475 deaths by June 2015. Human infections are primarily zoonotic, with clusters of human-to-human transmission, especially in healthcare settings. In a 2014 outbreak in Jeddah, 255 cases were reported, but infection prevention measures halted the outbreak. Genetic data showed widespread transmission of related viruses. The study analyzed viral genetic data from patients and HCWs at KFMC from February 1 to May 31, 2014, and available epidemiologic data. A time-resolved phylogenetic tree showed that the outbreak was part of a larger outbreak in Riyadh, involving other hospitals like PSMMC and KKUH. A zoonotic event occurred around December 31, 2013, with a 95% HPD interval of November 8, 2013–February 10, 2014. The outbreak was linked to multiple introductions of MERS-CoV into KFMC, with genetic diversity among patients. Epidemiologic data showed that the ER and MW-C were major transmission foci. HCWs with mild symptoms may have contributed to transmission. The study highlighted the need for complete genome analysis in outbreak investigations. The outbreak was linked to multiple introductions from outside the hospital, with some cases possibly from external sources. The study also emphasized the importance of understanding transmission pathways to minimize spread. The study had limitations, including the unavailability of archived specimens from patients outside KFMC and retrospective data collection. Despite these, the findings provided molecular epidemiologic data suggesting a large MERS outbreak involving multiple healthcare facilities in Riyadh, with ongoing human-to-human transmission over several months. The study demonstrated the feasibility and value of complete viral genome sequence analysis in outbreak investigations. The findings underscore the ongoing threat of MERS and the need for understanding transmission pathways to prevent future outbreaks.A MERS-CoV outbreak occurred at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, from March 29 to May 21, 2014, involving 45 patients, including 8 with external infections, 13 long-term patients, 23 healthcare workers (HCWs), and 1 with an indeterminate source. Molecular epidemiology showed that the outbreak was part of a larger outbreak in Riyadh, likely originating from a single zoonotic transmission event in December 2013. This indicated ongoing healthcare-associated transmission for 5 months. The study used genetic data to trace transmission chains and identify multiple external introductions, supporting or refuting suspected transmission pathways. MERS-CoV was first identified in 2012, with over 1,300 confirmed cases and 475 deaths by June 2015. Human infections are primarily zoonotic, with clusters of human-to-human transmission, especially in healthcare settings. In a 2014 outbreak in Jeddah, 255 cases were reported, but infection prevention measures halted the outbreak. Genetic data showed widespread transmission of related viruses. The study analyzed viral genetic data from patients and HCWs at KFMC from February 1 to May 31, 2014, and available epidemiologic data. A time-resolved phylogenetic tree showed that the outbreak was part of a larger outbreak in Riyadh, involving other hospitals like PSMMC and KKUH. A zoonotic event occurred around December 31, 2013, with a 95% HPD interval of November 8, 2013–February 10, 2014. The outbreak was linked to multiple introductions of MERS-CoV into KFMC, with genetic diversity among patients. Epidemiologic data showed that the ER and MW-C were major transmission foci. HCWs with mild symptoms may have contributed to transmission. The study highlighted the need for complete genome analysis in outbreak investigations. The outbreak was linked to multiple introductions from outside the hospital, with some cases possibly from external sources. The study also emphasized the importance of understanding transmission pathways to minimize spread. The study had limitations, including the unavailability of archived specimens from patients outside KFMC and retrospective data collection. Despite these, the findings provided molecular epidemiologic data suggesting a large MERS outbreak involving multiple healthcare facilities in Riyadh, with ongoing human-to-human transmission over several months. The study demonstrated the feasibility and value of complete viral genome sequence analysis in outbreak investigations. The findings underscore the ongoing threat of MERS and the need for understanding transmission pathways to prevent future outbreaks.