OBJECTIVES: Our aim was to describe the epidemiology and outcomes of multisystem inflammatory syndrome in children (MIS-C) in Latin America. METHODS: We conducted an observational, retrospective, and prospective multicenter study that gathered information from 84 participating centers across 16 Latin American countries between August 1, 2020 and June 30, 2022. RESULTS: Of the 1239 reported children with MIS-C, 84.18% were previously healthy. The most frequent clinical manifestation in our studied population was abdominal pain (N = 804, 64.9%), followed by conjunctival injection (N = 784, 63.3%). The median duration of fever at the time of hospital admission was 5 days and a significant number of subjects required admission to an intensive care unit (N = 589, 47.5%). Most of the subjects (N = 1096, 88.7%) were treated with intravenous immunoglobulin, whereas 76.7% (N = 947) were treated with steroids, of whom 10.6% (N = 100) did not receive intravenous immunoglobulin. The death rate attributed to MIS-C was 4.88%, with a rate of 3.39% for those initially diagnosed with MIS-C and 8.85% for those whose admission diagnosis was not MIS-C (P <0.001, odds ratio 2.76, 95% confidence interval 1.6-4.6). CONCLUSIONS: One of the most significant findings from our study was the death rate, especially in those not initially diagnosed with MIS-C, in whom the rate was higher. This highlights the importance of increasing awareness and making an earlier diagnosis of MIS-C in Latin America.