Our findings suggest that identifying vaccine-induced thrombotic thrombocytopenia (VITT) in observational data presents a substantial challenge.

Implementing VITT case definitions based on the co-occurrence of thrombosis with thrombocytopenia results in large and heterogeneous incidence rates in a cohort composed of patients with baseline characteristics that are different to the VITT cases reported after the coronavirus disease 2019 (COVID-19) vaccines.

We advise that further refinement of the case definition is needed before observational data can be reliably used to generate unbiased population-level effect estimates for VITT safety surveillance.