The outcomes of relapsed childhood acute lymphoblastic leukemia (ALL) in developed countries have improved over time as a result of risk-adapted, minimal residual disease-directed therapy, hematopoietic stem cell transplantation, and immunotherapy. There are few studies that have examined survival in relapsed childhood ALL in resource-limited countries. Therefore, this study aimed to assess the prognostic factors and survival outcome of relapsed childhood ALL in a major tertiary center in Southern Thailand. The medical records of patients with ALL aged <15 years between January 2000 and December 2019 were retrospectively reviewed. The Kaplan-Meier method was used to depict the overall survival (OS). A total of 472 patients with ALL were enrolled and relapsed ALL was found in 155 (32.8%) patients. Of these, 131 (84.5%) and 24 (15.5%) had B-cell and T-cell phenotypes, respectively. One hundred thirteen (72.9%) and 42 (27.1%) patients had early and late relapses, respectively. The most common site of relapse was bone marrow in 102 patients (65.8%). One hundred twenty-eight (82.6%) patients received treatment while 27 (17.4%) patients refused treatment. The 5-year OS of all relapsed patients was 11.9%. The 5-year OS among the patients with early relapse was significantly lower than in the patients with late relapse (5.3% vs. 29.1%, respectively, p <0.0001). Site and immunophenotype were not associated with survival of relapsed ALL. The median survival times among the patients who received and refused relapse chemotherapy were 11.8 and 3.1 months, respectively (p <0.0001). The relapse rate accounted for one third of patients with ALL with the 5-year OS of 12%. Early relapse and those who refused treatment were associated with poor survival outcome.