The objective was to compare the performance of the updated Charlson comorbidity index (uCCI) and classical CCI (cCCI) in predicting 30-day mortality in patients with Staphylococcus aureus bacteraemia (SAB). All cases of SAB in patients aged ⩾14 years identified at the Microbiology Unit were included prospectively and followed. Comorbidity was evaluated using the cCCI and uCCI. Relevant variables associated with SAB-related mortality, along with cCCI or uCCI scores, were entered into multivariate logistic regression models. Global model fit, model calibration and predictive validity of each model were evaluated and compared. In total, 257 episodes of SAB in 239 patients were included (mean age 74 years; 65% were male). The mean cCCI and uCCI scores were 3.6 (standard deviation, 2.4) and 2.9 (2.3), respectively; 161 (63%) cases had cCCI score ⩾3 and 89 (35%) cases had uCCI score ⩾4. Sixty-five (25%) patients died within 30 days. The cCCI score was not related to mortality in any model, but uCCI score ⩾4 was an independent factor of 30-day mortality (odds ratio, 1.98; 95% confidence interval, 1.05–3.74). The uCCI is a more up-to-date, refined and parsimonious prognostic mortality score than the cCCI; it may thus serve better than the latter in the identification of patients with SAB with worse prognoses.