Objective The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3‐PBX1 rearrangement. Patients All children in Hong Kong diagnosed with ALL with TCF3‐PBX1 rearrangement over the past two decades were included. Methods Six hundred and twenty‐four newly diagnosed patients with ALL from four consecutive studies were enrolled from 1997 to 2016. Patients carrying TCF3‐PBX1 rearrangement and patients at intermediate risk without the gene expression were compared for clinical characteristics, overall survival and event‐free survival (EFS). Results The TCF3‐PBX1 rearrangement was detected in 30 of 624 patients (4.8%). Results were consistent across the consecutive clinical trials employed in the past two decades. Compared with 239 intermediate risk patients without TCF3‐PBX1 rearrangement, the 5‐year overall survival and EFS for patients with TCF3‐PBX1 rearrangement was superior, with both at 100% (P = 0.12 and P = 0.029). Conclusion This population‐based study over the past 20 years demonstrated that patients with TCF3‐PBX1 rearrangement had favourable EFS compared with other intermediate risk patients treated with a similar chemotherapy backbone.