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Background: To explore the prognostic and therapeutic value of the age-adjusted Charlson Comorbidity Index (ACCI) for patients with obstructive sleep apnea (OSA) aged 60 years and older.Methods: Between January 2015 and October 2017, this multicenter, prospective, observational cohort study continuously enrolled 1183 older patients (age ≥60 years) with clinician-diagnosed OSA (sleep-laboratory-based overnight polysomnography) from sleep centers of six hospitals. Baseline demographics, clinical characteristics, sleep parameters, and medical history were obtained from electronic patient records, the ACCI was calculated, and participants were followed up prospectively to determine the primary outcome of all-cause mortality. Based on an ACCI cutoff of 4.5, participants were classified into the low-ACCI and high-ACCI groups and the receiver operating characteristic (ROC) curves were plotted. Kaplan–Meier survival analysis with log-rank test and Cox proportional hazards regression modeling was performed.Results: During a median 43-month follow-up, 63 (5.3%) patients died. ROC curves revealed an optimal ACCI cutoff of 4.5, and the area under the curve (AUC) of 0.70 [95% confidence interval (CI): 0.63–0.77] reached statistical significance (P<0.001). Kaplan–Meier survival analysis revealed 6-year survival rate of 56.04% and 92.17% for the high-ACCI and low-ACCI (ACCI ≥5 and <5; n=336 and n=847) groups, respectively. Regardless of sex or OSA severity, the ACCI was associated with the all-cause mortality risk of older OSA patients (log-rank, both P<0.001). After controlling for confounding variables, the mortality risk was 3.32 times (95% CI: 1.91–5.77) higher in the high-ACCI group than in the low-ACCI group. Multivariate Cox stepwise regression analyses indicated that total sleep time (TST), Mean Corpuscular Volume (MCV), and ACCI (aHR [95% CI]=1.258 [1.053–1.503], 1.047 [1.007–1.087], and 1.583 [1.384–1.815]; P=0.011, 0.019, and 0.000, respectively) were significant independent predictors of all-cause mortality.Conclusion: The ACCI is a predictor of all-cause mortality in older OSA patients (age≥60 years), with a higher ACCI indicating a higher mortality risk. The ACCI can guide clinical treatment selection for older OSA patients.