Objectives: Talaromyces marneffei (T. marneffei) is an opportunistic fungal infection (talaromycosis), which is common in subtropical regions and is a leading cause of death in HIV-1-infected patients. This study aimed to determine the characteristics and risk factors associated with hospital readmissions in HIV patients with T. marneffei infection in order to reduce readmissions. Methods: We conducted a retrospective study of admitted HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from 2012 to 2019. Kaplan-Meier analyses and Principal component analysis (PCA) were used to evaluate the effects of T. marneffei infection on patient readmissions. Additionally, univariate and multifactorial analyses, as well as Propensity score matching (PSM) were used to analyze the factors associated with patient readmissions. Results: HIV/AIDS patients with T. marneffei-infected had shorter intervals between admissions and longer lengths of stay than non-T. marneffei-infected patients, despite lower readmission rates. Compared with non-T. marneffei-infected patients, the mortality rate for talaromycosis patients was higher at the first admission. Among HIV/AIDS patients with opportunistic infections, the mortality rate was highest for T. marneffei at 16.2%, followed by cryptococcus at 12.5%. However, the readmission rate was highest for cryptococcus infection (37.5%) and lowest for T. marneffei (10.8%). PSM and Logistic regression analysis identified leukopenia and elevated low-density lipoprotein (LDL) as key factors in T.marneffei-infected patients hospital readmissions. Conclusions: The first admission represents a critical window to intervene in the prognosis of patients with T. marneffei infection. Leukopenia and elevated LDL may be potential risk factors impacting readmissions. Our findings provide scientific evidence to improve the long-term outcomes of HIV patients with T. marneffei infection. Author summary: Talaromyces marneffei is an opportunistic fungal infection primarily affecting individuals with impaired immune function, namely those with HIV-infected. Previous studies from Guangxi, China have reported approximately 17% mortality among HIV/AIDS patients with talaromycosis. Our study reveals a 10.8% readmission rate and a 16.2% mortality rate among HIV/AIDS patients who were exclusively infected with T. marneffei during the first admission. Understanding these key prognostic factors and the timing of intervention are crucial for clinicians to improve patient outcomes and reduce hospital readmissions. To address this issue, we conducted an extensive 8-year retrospective study involving 12,946 HIV/AIDS patients. Compared to the eight major common opportunistic infections, T. marneffei-infected patients had the lowest readmission rate, yet accounted for the highest mortality rate. Leucopenia and elevated LDL emerged as significant risks for increasing hospital readmissions. Importantly, our study highlights the critical window for intervening in talaromycosis prognosis–the first hospitalization. These findings have major clinical implications, enabling clinicians to implement effective treatments and interventions starting at first hospital admission to improve prognosis in HIV/AIDS patients with T. marneffei-infected. [ABSTRACT FROM AUTHOR]