Owing to the increased central nervous system (CNS) relapse risk in T-cell acute lymphoblastic leukaemia (ALL), it is unclear whether preventive cranial radiation (pCRT) can be safely omitted. In this study, pCRT was replaced by extended triple intrathecal therapy (TIT) in prednisone good early responders – medium-risk (MR) group, accounting for 76% of T-ALL patients. From 1989 to 2003, 143 T-ALL patients aged 1–18 years were enrolled in the Israel National Studies (INS) 89 (n = 84) and INS 98 (n = 59) trials, based on ALL-Berlin–Frankfurt–Munster (BFM) 86/90 and ALL-BFM 95 protocols, respectively. Five-year event-free survival (EFS) of the MR group in the INS 89 (n = 60) was 70 ± 5·9% and the INS 98 (n = 43), 83·7 ± 5·6% (P = 0·12); the cumulative incidence (CI) of any CNS relapse was 5·0 ± 2·8% and 2·3 ± 2·3% (P = 0·50), respectively. There was no difference in outcome between MR patients with a white blood cell count (WBC) ≥100 × 109/l treated with extended TIT (n = 17) or pCRT (n = 10). For all T-ALL patients, 5-year EFS was 61·9 ± 5·3% in INS 89 and 72·9 ± 5·8% in INS 98, (P = 0·21); the CI of any CNS relapse was 7·1 ± 2·8% and 1·7 ± 1·7% (P = 0·142), respectively. Outcome of T-ALL MR patients given extended TIT in the context of BFM-based protocols with long-term follow-up appeared to be comparable to studies in which a larger proportion of patients was irradiated, and was associated with low risk of CNS relapse, regardless of the WBC.