Overall survival rates of children with acute lymphoblastic leukaemia (ALL) in high-income countries approach 90%. Treated on the same protocols, outcomes in India, were ∼65%. The Indian Childhood Collaborative Leukaemia (ICiCLe) group used genetics and measurable residual disease (MRD) to categorise B-cell precursor (BCP) ALL as standard (SR), intermediate (IR) and high-risk (HR) to receive increasing intensity of therapy. T-ALL were treated uniformly. Data on risk stratification, deaths and relapses were collected annually. 2695 patients aged 1–18 years were enrolled between January 2013 and May 2018. Induction deaths were significantly lower in SR patients (p = 0·002) compared to others. At a median 61 (59–62) months, the 4-year event free and overall survival was 76% (72–79%) and 88% (85–90%) in SR; 70% (66–74%) and 80% (77–83%) in IR; 61% (51–64%) and 73% (70–76%) in HR; and 69% (62–75%) and 77% (70–83%) in T-ALL patients (p < 0·0001). For BCP-ALL, regression analyses showed age, white cell count, bulky disease, high risk genetics and treating centre as independent prognostic variables. The cumulative incidence of treatment deaths (TRD) and relapses at centres varied from 2% (1–5) to 13% (10–17) (p ≤ 0·0001); and 21% (17–26) to 45% (39–51) (p ≤ 0·0001) respectively with significant differences in proportion of BCP-ALL patients with MRD ≥ 0·01% (p = 0·0007) and time to relapse (p = 0·0001). Risk stratified directed reduced intensity treatment and collaboration decreases treatment deaths and relapses. Standardisation of genetic and MRD tests across centres and access to high quality drugs will lead to further improvements in survival. DBT-Wellcome; 10.13039/501100000732 UKIERI , TCS Foundation.