Identify the frequency of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C) and the outcomes that are typically linked with them. In-depth analysis of data from the Viral Infection and Respiratory Illness Universal Study Registry, a prospective observational multicenter international cohort study of children admitted to hospitals with acute COVID-19 or MIS-C from March 2020 through November 2020. Serious cases of COVID-19 were a key indicator of success. In both the full cohort and a subset of patients with MIS-C, multivariable models were used to examine the correlation between GI involvement and the primary composite outcome. Mortality and hospital length of stay (>75th) were secondary outcomes. About 500 (63.3%) of the total number of 789 patients had GI involvement. Of those, 392 (49.6%) became seriously ill, and 18 (2.3% of the total) died. Those affected in the gastrointestinal tract had a higher median age (by 8 years) and a higher rate (18.2%) of underlying GI comorbidities. In individuals with MIS-C, gastrointestinal distress and liver abnormalities were more common. Acute COVID-19 was not related to the primary or secondary outcomes in the adjusted multivariable models. Even though gastrointestinal (GI) involvement was common in patients with MIS-C, researchers found no correlation between GI involvement and either primary or secondary outcomes. Hospitalized children with acute COVID-19 and MIS-C often show gastrointestinal symptoms. There is no correlation between GI involvement and a more severe disease, longer hospital stay, or death in patients with acute COVID-19 or MIS-C.