Background Acute infection leads to substantial mortality in the nonagenarian population. However, the predictive efficacies of functional status and biochemical indexes for in-hospital mortality in these patients remain to be determined. Methods A single-center, retrospective cohort study was performed. Consecutive nonagenarian patients who were admitted to our department from January 1, 2014 to December 31, 2016 for acute infectious diseases were included. Baseline data for medical history, functional status, and biochemical indexes were obtained on admission. The outcomes of these patients during hospitalization were recorded. Predictors of in-hospital mortality were identified via logistic regression analyses. Results A total of 162 patients were included, and 46 patients died (17.2%) during hospitalization. Univariate analysis showed that the prevalence rates of atrial fibrillation (32.1%) and malignant disease (26.5%) were higher in nonagenarian patients who died during hospitalization than in those who discharged. Multivariate logistic regression analyses identified malignant disease (odds ratio [OR] 2.73, 95% confidence interval [CI]: 1.10-6.78), ADL category (OR 0.82, 95% CI: 0.75-0.89) and serum albumin (OR 0.86, 95%CI 0.78-0.95) as independent predictors of in-hospital mortality in nonagenarian patients hospitalized for acute infection. Conclusions Functional impairment as well as serum albumin may be independent predictors of in-hospital mortality in nonagenarian patients hospitalized for acute infectious diseases. Stratification of patients according to Barthel Index score and serum albumin is very necessary.