Australian Genomics Health Alliance Acute Care Flagship, et al. - The performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system was prospectively evaluated via performing a multisite descriptive feasibility study including 12 Australian hospitals and 2 laboratories. Ultra-rapid genomic testing was performed on 108 critically ill infants and children with suspected monogenic conditions. These cases had median age of 28 days (range, 0 days to 17 years); 34% of them were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. Among these cases, the mean time to genomic test report was 3.3 days and the molecular diagnostic yield was 51%. The ultra-rapid exome sequencing result was identified influencing clinical management in 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis. Findings support the feasibility of performing ultra-rapid genomic testing in a public setting for critically ill pediatric patients with suspected monogenic conditions in Australia.