BACKGROUNDPeripheral venous catheter-associated Staphylococcus aureus bacteraemia (PVC-SAB) is a potentially life-threatening nosocomial infection.AIMThis cohort study aims to identify the risk factors associated with its mortality and complications.METHODSRetrospective analysis of a prospective cohort study conducted at two tertiary-care hospitals in Spain. Adult patients admitted between January 2011 and July 2019 which developed PVC-SAB during their hospital stay were included. Primary outcome was all-cause 30- and 90-day mortality. Secondary outcomes were sepsis or septic shock at the onset of bacteraemia, metastatic infection and length of hospital stay. Univariate and multivariate analyses were performed.FINDINGSA total of 256 PVC-SAB were diagnosed in 243 patients between 2011 and 2019. Thirty-day and 90-day all-cause mortality were 18.3% and 24.2%, respectively. Lack of susceptible antibiotic administration the day after blood culture collection (odds ratio: 4.14; 95% confidence interval: 1.55-11.03; P = 0.005), sepsis and complicated bacteraemia were identified as independent risk factors for 30- and 90-day mortality; meticillin-resistant S. aureus bacteraemia was identified as an independent risk factor only for 30-day mortality and functional dependence only for 90-day mortality. Persistent bacteraemia and sepsis were associated with septic metastases, which significantly increased hospital stay, and endocarditis. A greater proportion of patients experiencing septic shock were subsequently institutionalized compared to those without.CONCLUSIONPVC-SAB remains linked to high mortality rates. Prompt administration of appropriate antibiotics is crucial for lowering mortality. A comprehensive diagnostic approach is essential, especially in patients with persistent bacteraemia and implanted cardiovascular devices, to rule out metastatic complications and endocarditis.