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Summary: Risk‐adapted therapy is recommended to prevent major clinical complications, such as thrombo‐haemorrhagic events, in patients with essential thrombocythaemia (ET). In this study, we analysed the association between non‐driver gene mutations and thrombo‐haemorrhagic events in 579 patients with ET. ASXL1 and TP53 mutations were frequently identified in patients with ET complicated by thrombosis (22.7% and 23.1%, respectively), and the DNMT3A mutation was frequently identified in patients who experienced haemorrhage (15.2%). Multivariate analyses of thrombosis‐free survival (TFS) revealed that ASXL1 and TP53 mutations are associated with thrombosis (hazard ratio [HR] = 3.140 and 3.752 respectively). Patients harbouring the ASXL1 or TP53 mutation had significantly worse TFS rates than those without mutation (p = 0.002 and p < 0.001 respectively). Furthermore, JAK2V617F‐mutated patients with accompanying ASXL1 mutations showed significantly shorter TFS compared with those without ASXL1 mutations (p = 0.003). Multivariate analyses of haemorrhage‐free survival (HFS) revealed that the DNMT3A mutation (HR = 2.784) is associated with haemorrhage. DNMT3A‐mutated patients showed significantly shorter HFS than those without the mutation (p = 0.026). Non‐driver gene mutations should be considered in treatment strategies and may provide important information for personalised treatment approaches. [ABSTRACT FROM AUTHOR]