Background Comorbidity is related to poor health results in chronic heart failure (HF). Aims The purpose of the study was to assess whether a high Charlson Comorbidity Index score (CCI) relates to 1 year mortality after a first hospitalization for acute HF (AHF). Methods We reviewed the medical records of 897 patients > 65 years of age admitted within a two-year period because of a first episode of AHF. We analyzed two groups: low (CCI ≤ 2) and high (CCI > 2) comorbidity. Results Patients’ mean CCI was 2.2 ± 1.7; 344 patients (38.35%) had a CCI > 2. 1-year all-cause mortality rate in the high comorbidity group was 32.6%, worse than that among low comorbidity group patients (23.7%, p  = 0.002). Cox multivariate analysis identified a CCI > 2 as an independent risk factor for 1-year mortality ( p  = 0.002; HR: 1.525; CI 95% 1.161–2.003), along with older age, history of arterial hypertension, and higher admission heart rate and serum potassium values. Analyzing CCI as a continuous variable, the association remained is also significant ( p  = 0.0001; HR 1.145; CI 95% 1.069–1.854). Conclusions Higher global comorbidity (CCI > 2) at the time of a first hospitalization because of AHF is an independent predictor of mid-term post-discharge mortality among elderly HF patients.