Extracorporeal membrane oxygenation (ECMO) provides lifesaving circulatory support and gas exchange, although hematologic complications are frequent. The relationship between ECMO and severe thrombocytopenia (platelet count <50 × 10⁹/L) remains ill-defined. We performed a cohort study of 67 patients who received ECMO between 2016 and 2019, of which 65.7% received veno-arterial (VA) ECMO and 34.3% received veno-venous (VV) ECMO. All patients received heparin and 25.4% received antiplatelet therapy. In total, 23.9% of patients had a thrombotic event and 67.2% had a hemorrhagic event. 38.8% of patients developed severe thrombocytopenia. Severe thrombocytopenia was more common in patients with lower baseline platelet counts and increased the likelihood of thrombosis by 365% (OR 3.65, 95% CI 1.13–11.8, P = .031), while the type of ECMO (VA or VV) was not predictive of severe thrombocytopenia (P = .764). Multivariate logistic regression controlling for additional clinical variables found that severe thrombocytopenia predicted thrombosis (OR 3.65, CI 1.13–11.78, P = .031). Over a quarter of patients requiring ECMO developed severe thrombocytopenia in our cohort, which was associated with an increased risk of thrombosis and in-hospital mortality. Additional prospective observation is required to clarify the clinical implications of severe thrombocytopenia in the ECMO patient population.