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Objective: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia. Methods: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C. Results: A total of 28 children presented MIS-C criteria. The median age was 7 years. Other than fever (100%) (onset 4 days prior to admission), the most frequent clinical features were gastrointestinal (86%) and mucocutaneous (61%). Notably, 14 (50%) children had Kawasaki-like symptoms. The most frequent echocardiographic abnormalities were pericardial effusion (64%), valvular involvement (68%), ventricular dysfunction (39%), and coronary artery abnormalities (29%). In addition, 75% had lymphopenia. All had at least one abnormal coagulation test. Most received intravenous immunoglobulin (89%), glucocorticoids (82%), vasopressors (54%), and antibiotics (64%). Notably, 61% had a more severe form of the disease and were admitted to an intensive care unit (median 4 days, mean 6 days); the severity predictors were patients with the inflammatory/MIS-C phenotype (OR 26.5; 95%CI 1.40–503.7; p=0.029) and rash (OR 14.7; 95%CI 1.2–178.7; p=0.034). Two patients had macrophage activation syndrome. Conclusions: Coronary artery abnormalities, ventricular dysfunction, and intensive care unit admission were frequent, which needs to highlight the importance of early clinical suspicion. [ABSTRACT FROM AUTHOR]