The present study aimed to investigate the efficacy and safety for alternate application of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) combined with idarubicin (IDA)/daunorubicin (DNR) in treatment of acute promyelocytic leukemia (APL). A total of 72 ALP patients were divided into the low/medium risk and high risk groups according to the WBC and PLT levels. All APL patients received induction therapy, consolidation therapy and maintenance therapy in treatment under careful nursing monitoring. The complete response (CR) rate was 87.5% (63/72), with 95.12% (39/41) in the low/medium risk group, which was markedly higher than the 77.42% (24/31) high risk group. The PML/RAR α fusion negative rate was also markedly higher in the low/medium risk group (95.12%, 39/41) than the high risk group (77.42%, 24/31). The duration for PML/RAR α fusion negative was also significantly shorter in the low/medium risk group. Recurrence was found in cases in the low/medium risk group, markedly lower than cases in the high risk group. The overall survival (OS) time was markedly longer in low/medium risk patients high. Alternate application of the combination strategy could achieve well CR rate with less complications. And patients with low/medium risk had better clinical outcomes and prognosis than high risk patients.