Abstract: Objective To analyze the clinical effectiveness of decitabine combined with CAG regimen (cytanabine + acclarithromycin + granulocyte colony-stimulating factor, DCAG regimen) and programmed death receptor 1 (PD-1) inhibitor (tirelizumab or sindilizumab) in the treatment of relapsed/refractory acute myeloid leukemia (AML). Methods A total of 58 patients who were diagnosed with relapsed/refractory AML in the Affiliated Hospital of Xuzhou Medical University from January 2018 to May 2021 were enrolled. They were divided into two groups: a decitabine combined with CAG (DCAG) regimen group (n=40), and a PD-1 inhibitor combined with DCAG regimen (P-DCAG) group (n=18). The objective response rate (ORR), complications, biochemical indicators and prognosis of the two groups were compared between the two groups. Results In the P-DCAG group, the proportion of patients who received chemotherapy ≥five times was significantly higher than that in the DCAG group, while the proportion of patients not receiving transplantation was significantly lower than that in the DCAG group (P<0.05). There were no significant differences in ORR, complete response (CR), partial response (PR), no response (NR), 1-year progression-free survival, median overall survival and median progression-free survival between the two groups (P>0.05). The mean survival time was 17 months for the P-DCAG group and 11 months for the DCAG group. The 1-year overall survival rate in the P-DCAG group (77.78%) was higher than that in the DCAG group (52.50%). For patients aged ≥60 years, the progression-free survival (PFS) of the P-DCAG group was remarkably longer than that of the DCAG group (P<0.05). The P-DCAG group had a lower incidence of myelosuppression than the DCAG group (P<0.001). Conclusions Compared with DCAG regimen, P-DCAG regimen may improve the overall prognosis of patients, providing a possible option for the treatment of AML.