BACKGROUND Since the first isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in 2012, sporadic cases, clusters, and sometimes large outbreaks have been reported. OBJECTIVE To describe the recent (2015) MERS-CoV outbreak at a large tertiary care hospital in Riyadh, Saudi Arabia. METHODS We conducted an epidemiologic outbreak investigation, including case finding and contact tracing and screening. MERS-CoV cases were categorized as suspected, probable, and confirmed. A confirmed case was defined as positive reverse transcription polymerase chain reaction test for MERS-CoV. RESULTS Of the 130 suspected cases, 81 (62%) were confirmed and 49 (38%) were probable. These included 87 patients (67%) and 43 healthcare workers (33%). Older age (mean [SD], 64.4 [18.3] vs 40.1 [11.3] years, P<.001), symptoms (97% vs 58%, P<.001), and comorbidity (99% vs 42%, P<.001) were more common in patients than healthcare workers. Almost all patients (97%) were hospitalized whereas most healthcare workers (72%) were home isolated. Among 96 hospitalized cases, 63 (66%) required intensive care unit management and 60 (63%) required mechanical ventilation. Among all 130 cases, 51 (39%) died; all were patients (51 [59%]) with no deaths among healthcare workers. More than half (54%) of infections were believed to be caught at the emergency department. Strict infection control measures, including isolation and closure of the emergency department, were implemented to interrupt the chain of transmission and end the outbreak. CONCLUSION MERS-CoV remains a major healthcare threat. Early recognition of cases and rapid implementation of infection control measures are necessary. Infect Control Hosp Epidemiol 2016;1-9.