Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by microvascular hemolytic anemia and thrombocytopenia. To further our understanding of the clinical characteristics of TA-TMA in pediatric patients, we retrospectively analyzed 20 pediatric patients with TA-TMA from August 1, 2016 to December 31, 2021 in our center. During this period, 209 patients received allo-HSCT in our department, 20 (9.6%) of whom developed TA-TMA. TA-TMA was diagnosed at a median of 94 (7–289) days post-HSCT. Eleven (55%) patients had early TA-TMA within 100 days post-HSCT, while the other 9 (45%) patients had TA-TMA thereafter. The most common symptom of TA-TMA was ecchymosis (55%), while the main signs were refractory hypertension (90%) and multi-cavity effusion (35%). Five (25%) patients had central nervous system symptoms (convulsions and lethargy). Median follow-up time was 8 (1–26) months. All 20 patients had progressive thrombocytopenia, with 16 patients receiving transfusion of platelets that was ineffective. Ruptured red blood cells were visible in only two patients with peripheral blood smears. Cyclosporine A or Tacrolimus (CNI) dose was reduced once TA-TMA was diagnosed. Nineteen cases were treated with low-molecular-weight heparin, 17 patients received plasma exchange, and 12 patients were treated with rituximab. TA-TMA-related mortality percentage in this study was 45% (9/20). Of the 11 patients who were effectively treated initially, 4 died of sepsis and acute respiratory failure. In conclusion, platelet decline and/or ineffective transfusion post-HSCT should be considered an early indicator of TA-TMA in pediatric patients. TA-TMA in pediatric patients may occur without evidence of peripheral blood schistocytes. Aggressive treatment is required once diagnosis is confirmed, but the long-term prognosis is poor.