The vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. In this study, the outcomes of patients with MSSA bacteraemia with a vancomycin MIC ≥ 1.5 mg/L were assessed. A prospective cohort of patients with MSSA bacteraemia in two tertiary-care hospitals was collected. The vancomycin MIC was determined by Etest. Staphylococcus aureus strains were categorised as low (<1.5 mg/L) or high (≥1.5 mg/L) vancomycin MIC. First- and second-line treatments were recorded and classified as optimal, appropriate and inappropriate. The primary endpoint was 30-day mortality. A total of 250 patients with S. aureus bacteraemia were analysed, of whom 64 (25.6%) had strains with a high vancomycin MIC. History of dialysis (P = 0.001) and ultimately fatal disease (P = 0.005) were associated with strains with a high vancomycin MIC. The 30-day mortality was 24.7% (46/186) in patients with a low vancomycin MIC versus 28.1% (18/64) in patients with a high vancomycin MIC (P = 0.592) and did not differ significantly after adjustment for the appropriateness of the antibiotic treatment. Patients with a high vancomycin MIC were less frequently associated with complicated bacteraemia (15.6% vs. 39.2%; P = 0.001). In conclusion, vancomycin MIC ≥ 1.5 mg/L was not associated with 30-day mortality but was associated with uncomplicated bacteraemia in MSSA bacteraemia, regardless of the first- and second-line treatment.