BACKGROUND: Enterovirus 68 (EV-D68) causes acute respiratory tract illness in epidemic cycles, most recently in Fall 2014, but clinical characteristics of severe disease are not well reported. OBJECTIVES: Children with EV-D68 severe respiratory disease requiring pediatric intensive care unit (PICU) management were compared with children with severe respiratory disease from other enteroviruses/rhinoviruses. STUDY DESIGN: A retrospective review was performed of all children admitted to Children\'s Mercy Hospital PICU from August 1-September 15, 2014 with positive PCR testing for enterovirus/rhinovirus. Specimens were subsequently tested for the presence of EV-D68. We evaluated baseline characteristics, symptomatology, lab values, therapeutics, and outcomes of children with EV-D68 viral infection compared with enterovirus/rhinovirus-positive, EV-D68-negative children. RESULTS: A total of 86 children with positive enterovirus/rhinovirus testing associated with respiratory symptoms were admitted to the PICU. Children with EV-D68 were older than their EV-D68-negative counterparts (7.1 vs. 3.5 years, P=0.01). They were more likely to have a history of asthma or recurrent wheeze (68% vs. 42%, P=0.03) and to present with cough (90% vs. 63%, P=0.009). EV-D68 children were significantly more likely to receive albuterol (95% vs. 79%, P=0.04), magnesium (75% vs. 42%, P=0.004), and aminophylline (25% vs. 4%, P=0.03). Other adjunctive medications used in EV-D68 children included corticosteroids, epinephrine, and heliox; 44% of EV-D68-positive children required non-invasive ventilatory support. CONCLUSIONS: EV-D68 causes severe disease in the pediatric population, particularly in children with asthma and recurrent wheeze; children may require multiple adjunctive respiratory therapies.