Measurable residual disease (MRD) was evaluated using high-throughput sequencing (HTS) of the IGH and TRG genes or flow cytometry following induction chemotherapy in 619 paediatric patients with newly diagnosed B cell acute lymphoblastic leukaemia (B-ALL). Using an MRD threshold of 0.01%, the 5-year event-free survival (EFS) and overall survival were similar regardless of whether MRD had been determined by HTS or flow cytometry. For 55 patients, MRD was >0.01% according to HTS, but negative by flow cytometry. These patients had worse 5-year EFS than those with MRD >0.01% according to HTS. Thus, HTS has a higher analytical sensitivity than flow cytometry for the detection of MRD after induction chemotherapy in paediatric B-ALL.