Multisystem inflammatory syndrome in children (MIS-C) is a rare, presumed post-infectious hyperimmune response occurring approximately 2-4 weeks following exposure to SARS-CoV-2. The majority of children presenting with this disease are previously asymptomatic for coronavirus disease 2019 (COVID-19) and have no underlying medical conditions. Individuals with MIS-C experience complications of the cardiovascular system including cardiogenic shock and heart failure, acute respiratory failure, severe systemic inflammation, and disorders of the nervous, gastrointestinal, and mucocutaneous systems, often requiring lengthy stays in the intensive care unit (ICU), mechanical ventilation, and extensive therapeutic interventions. An analysis of the characteristics and outcomes of MIS-C and COVID-19 may help clinicians better diagnosis and treat these illnesses, improving outcomes for infected individuals. Over 2,000 case reports of COVID-19 and MIS-C from 66 pediatric hospitals in 31 U.S. states were collected via the Overcoming COVID-19 surveillance network. These reports included underlying conditions, presenting symptoms, laboratory values, clinical characteristics during hospitalization, and outcomes. Compared to children developing only COVID-19, patients with MIS-C were more likely to be between 6 to 12 years old, be non-Hispanic Black, have no underlying medical conditions, and have severe inflammation and cardiovascular involvement. Reassuringly, 91% of MIS-C patients with decreased cardiovascular output returned to normal within 30 days. Additionally, it was found that neurological involvement occurred in 22% of patients, with 2.5% developing life-threatening conditions including stroke, encephalopathy, and cerebral edema. These findings may improve our understanding of the differences between MIS-C and COVID-19 in children, although the long-term consequences of these diseases are unknown.