Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a postinfectious condition identified during the COVID-19 pandemic with specific Centers for Disease Control and Prevention and WHO criteria. Theoretical concerns have been raised whether MIS-C might also occur after COVID-19 vaccination, as the pathogenesis of MIS-C is not yet entirely understood. We present a woman in her late teens who developed MIS-C after having received two doses of Pfizer BioNTech COVID-19 vaccine 12 weeks prior, in the setting of documented anti-spike SARS-CoV-2 IgG positive, antinucleocapsid SARS-CoV-2 IgG negative, and multiple negative surveillance SARS-CoV-2 PCRs done in the 12-week period prior to development of MIS-C. While vaccination remains safe and critical in controlling the pandemic, it may be considered as a potential trigger for MIS-C in patients with no history of infection. Further surveillance is necessary to determine whether MIS-C will emerge as a confirmed adverse event after COVID-19 vaccination.