Antithrombotic drugs are consistently involved in medication-related adverse events (MRAEs) in hospitalized patients. We aimed to estimate the antithrombotic-related adverse event (ARAE) incidence between 2008 and 2016 and analyse their clinical context in hospitalized patients in The Netherlands. A post-hoc analysis of three national studies, aimed at adverse event (AE) identification, was performed. Previously identified AEs were screened for antithrombotic involvement. Crude and multi-level, case-mix adjusted ARAE and MRAE incidences were calculated. Various contextual ARAE characteristics were analysed. ARAE incidence between 2008 and 2016 decreased significantly in in-hospital deceased patients from 1.20% (95% confidence interval (CI): 0.63-2.27%) in 2008 to 0.54% (95% CI: 0.27-1.11%) in 2015/2016 (p = 0.02). In discharged patients ARAE incidence remained stable. By comparison, overall MRAE incidence remained stable for both deceased and discharged patients. Most ARAEs involved Vitamin-K antagonists (VKAs). Preventable ARAEs occurred more during weekends and with increasing multidisciplinary involvement. Antiplatelet and combined antithrombotic use seemed to be increasingly involved in ARAEs over time. ARAE incidence declined by 55% in deceased patients between 2008 and 2016. Opportunities for improving antithrombotic safety should target INR monitoring and care delivery aspects such as multidisciplinary involvement and weekend care. Future ARAE monitoring for the involvement of antiplatelet, combined antithrombotic and direct oral anticoagulant (DOAC) use is recommended.