Enterovirus-D68(EV-D68), first isolated in California in 1962 [1], has appeared biennially in the United States since the first reported nationwide outbreak in 2014, with outbreaks of different intensity occurring in late summer and early fall [2,3]. The clinical manifestations of EV-D68 infection range from mild to severe respiratory illness, especially in children with asthma who have shown to be at higher risk for severe EV-D68 infection [2,4]. In addition, EV-D68 has been associated with neurologic manifestations primarily acute flaccid myelitis (AFM) [4]. The circulation of EV-D68 in 2020 was lower than anticipated based on prior biennial trends, likely due to the widespread use of COVID-19 mitigation measures [5]. Nationwide Children's Hospital (NCH) in Columbus, Ohio, experienced an outbreak in 2014 and 2018 with a low activity period in 2016 [6]. Although low circulation of EV-D68 was identified in the US in 2020, we did not detect any cases at our institution. During summer 2022, EV-D68 re-emerged in the US causing respiratory symptoms [7]. The objective of this study is to describe the clinical and molecular characteristics of children hospitalized at NCH with EV-D68 infection during the 2022 outbreak.