Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of May 4, 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients ≥18 and <18 (including <3) years old were treated in first relapse (26.6% and 26.7% [<3 years old: 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [<3 years old: 15.5%]) with 17.6% and 11.6% [< 3 years old: 13.8%] having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% [<3 years old: 13.8%] having low disease burden (>0 to <5% BM blasts). Among patients with ≥12 months post-infusion follow-up (N=578; median follow-up 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. Twelve-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, while 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (<18 years) and disease burden (<50% BM blasts) were associated with better outcomes. Prior inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden prior to infusion. Any-grade CRS and neurotoxicity were lower in patients <3 years old. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.