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Thrombotic Thrombocytopenia Syndrome (TTS) has emerged as a new adverse event following immunization in individuals vaccinated with COVID-19 non-replicant adenovirus vector-based vaccines (AstraZeneca COVID-19 ChAdOx-1 vaccine and Johnson & Johnson (J&J) Janssen COVID-19 Ad26.COV2-S vaccine). TTS is a serious and life-threatening adverse event. WHO has issued this interim emergency guidance to increase awareness about TTS in the context of COVID-19 vaccination and help healthcare providers in the assessment and management of potential TTS cases. Knowledge about TTS following vaccination with a COVID-19 adenovirus vector-based vaccine is rapidly evolving. WHO will continue to monitor the situation closely for any changes that may affect this interim guidance and will update the guidance as needed.