: Due to the progress made in all areas of research, pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) now have an average overall survival rate of 90%. There are still discrepancies between high-income countries and limited-resource centers. The aim of this study was to analyze prognostic factors and outcome parameters in a 223-patient cohort from a single center in Romania, treated with two adapted BFM protocols. : The patients diagnosed with ALL in our center were enrolled in this study from January 2016 to December 2022 and subsequently followed up until December 2024. The patients were treated first according to the ALL IC BFM 2009 protocol until June 2019 and afterwards with the ALL AIEOP BFM 2017 protocol starting with July 2019. The prognostic factors were analyzed in both subgroups and the outcomes were measured: event-free survival (EFS), overall survival (OS), cumulative incidence of relapse (CIR), relapse-free survival (RFS) and non-relapse mortality (NRM). : The comparison between the two subgroups revealed that every parameter improved over time: complete remission after induction (87.75% vs. 80.7%), early deaths (3.92% vs. 5.78%), deaths in remission (4.08% vs. 5.26%), 5-year EFS (73.79% vs. 70.22%), 5-year CIR (18.36% vs. 19.04%), 5-year RFS (81.76% vs. 80.97%), 5-year NRM (7.85% vs. 10.77%), and 5-year OS (88.18% vs. 82.54%). Whereas for the standard-risk group, events such as relapse or death were isolated, for intermediate-risk patients, the events were limited to a small number and did not significantly influence the overall results, and for high-risk children, the results improved significantly between the two subgroups. The worst outcomes were observed in patients with the BCR::ABL1 fusion gene, T-cell phenotype, and in teenagers, compared to the ETV6::RUNX1 fusion gene, B precursor ALL, and in smaller children, respectively. : The 5-year OS increased in our center from 82.54% to almost 90%, with the most substantial finding being the survival rate for high-risk patients, now reaching up to 80%. The prognostic factors were age at diagnosis, genetic characteristics, and response to treatment, especially prednisone sensibility.