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Objectives To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts. Methods All children (1 month– 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C. Results Thirty children with median age of 24 (interquartile range (IQR)1–192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis. Conclusions Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes.