Objective　To analyze the in vitro yeast-phase drug susceptibility testing of 82 Talaromyces marneffei (TM) strains isolated at Yunnan Infectious Disease Hospital and their association with patient therapeutic outcomes. The study aims to investigate the antifungal resistance breakpoint for TM through in vitro susceptibility tests, evaluate the stability of the susceptibility testing methods, and assess the correlation between in vitro susceptibility test results and different clinical outcomes in HIV/AIDS patients with TM. This research provides a theoretical basis for the clinical selection of highly effective and low-toxicity antifungal drugs in treating HIV/AIDS with TM infection and aims to improve the clinical treatment quality. Methods　Clinical data from 82 HIV/AIDS patients co-infected with TM from 2017 to 2021 were retrospectively collected. The minimum inhibitory concentration (MIC) of TM strains from these patients was tested using the microdilution method at Yunnan Provincial Infectious Disease Hospital. Patients were divided into two groups based on therapeutic outcomes: good and poor. Statistical analyses were performed on epidemiological data, clinical characteristics, laboratory data, and treatment regimens between the two groups. Correlations between different MIC results and therapeutic outcomes were analyzed, and independent risk factors affecting prognosis were identified using multivariate logistic regression. The predictive value of the diagnostic indicators was assessed using the Receiver Operating Characteristic (ROC) curves. Results　Clinical efficacy: Out of the 82 patients, 38 had good outcomes and 44 had poor outcomes. Univariate analysis showed statistically significant differences (P<0.05) in abnormal imaging features, CD4+T lymphocyte count, duration of antifungal therapy, white blood cell (WBC) count, total protein (TP), albumin (ALB), and use of itraconazole. Patients who received itraconazole had better outcomes, with statistically significant differences (P<0.05). In vitro susceptibility testing: MICs for 82 TM strains were <4 to 4 mg/L for 5-fluorocytosine, <0.5 to 0.5 mg/L for amphotericin B, <1 to 8 mg/L for fluconazole, <0.125 mg/L for itraconazole, and <0.06 to 0.06 mg/L for voriconazole. There were no statistical differences in efficacy among patients with different susceptibility results for the same drug. Prognostic model: A significantly reduced CD4+T cell count was an independent risk factor for poor TM treatment outcomes, with a ROC curve area under the curve (AUC) of 0.983 (95%CI: 0.963-1.000), specificity of 0.955, and sensitivity of 0.919. Conclusion　The tested TM strains showed good sensitivity to all five antifungal drugs. Sequential treatment with itraconazole can improve patient prognosis, and CD4+T cell count is an independent risk factor affecting the prognosis of patients with TM infection.