A single-center retrospective study analyzed 132 patients with newly diagnosed acute promyelocytic leukemia (APL) from June 2017 to January 2023. The rate of premature death (ED) was 12.88% (17 patients), with bleeding as the main cause. Multivariate analysis identified three independent risk factors for ED: high white blood cell count (WBC > 201 × 10^9/L), prolonged prothrombin time (PT), and CD2 positivity. Severe thrombocytopenia was not an independent predictor, probably due to aggressive platelet transfusion. Elevated levels of lactate dehydrogenase (LDH) were associated with worse overall survival (OS). All relapses in high-risk patients involved the central nervous system (CNS). The study highlights the need for rapid diagnosis, risk-adapted treatment, and comprehensive care including management of coagulopathy and CNS prophylaxis in high-risk patients.