BACKGROUND: Enterovirus D68 (EV-D68) causes asthma-like respiratory infection in children. Several EV-D68 outbreaks have been reported worldwide since the largest outbreak occurred in the United States in 2014. We experienced an accumulation of pediatric cases with asthma-like respiratory illness in Niigata, Japan, in 2018. STUDY DESIGN: To determine whether EV-D68 was responsible for the case accumulation, this prospective observational study evaluated children hospitalized in 1 of 8 hospitals with asthma-like respiratory illness in Niigata, Japan, during October and November 2018. Diagnoses were made by EV-D68-specific RT-PCR using nasopharyngeal samples. The clade was identified by sequence analyses, and a phylogenetic tree was created. To evaluate seasonal variation, data from pediatric cases with asthma-like respiratory illness in 2018 were retrospectively analyzed. RESULTS: In 2018, 114 children were hospitalized with asthma-like respiratory illness in October and November, and 47 nasopharyngeal samples were collected. EV-D68 was detected in 22/47 (47%) patients during the study period. The phylogenetic tree revealed that all strains belonged to the clade B3 branch, which has been detected worldwide every 2 years since 2014. CONCLUSIONS: EV-D68 was the associated pathogen for asthma-like respiratory illness in children in Japan in 2018. Clade B3, the dominant clade in outbreaks worldwide, was responsible for the outbreak. Detection and detailed virologic analysis of EV-D68 is important as part of worldwide surveillance, as it will aid in understanding the epidemiologic characteristics of EV-D68 infection.