Cefazolin treatment failures have been described for bacteraemia caused by methicillin-susceptible Staphylococcus aureus (MSSA) with type A β-lactamase and inoculum effect (InE). We investigated the prevalence of blaZ (β-lactamase) gene types and a cefazolin InE among MSSA blood isolates in South Korea and evaluated their association with specific genotypes. The clinical impact of the cefazolin InE was also evaluated. A total of 220 MSSA isolates were collected from a prospective cohort study of S. aureus bacteraemia. A pronounced InE with cefazolin was defined as a ≥4-fold increase in the minimum inhibitory concentration (MIC) between a standard and high inoculum, resulting in a non-susceptible MIC. Sequencing of blaZ and multilocus sequence typing (MLST) were performed. Clinical outcomes were assessed in 77 patients treated with cefazolin. The blaZ gene was detected in 92 % of the 220 MSSA isolates. Type C β-lactamase was the most common (53 %), followed by type B (20 %) and type A (17 %). Certain genotypes were significantly associated with specific β-lactamase types (notably, ST30 and type A β-lactamase). A pronounced cefazolin InE was observed in 13 % of isolates. Most of these (79 %) expressed type A β-lactamase and ST30 was the predominant (55 %) clone amongst them. Cefazolin treatment failure was not observed in patients infected with strains exhibiting a pronounced InE. These strains had no impact on other clinical outcomes. In conclusion, the prevalence of a pronounced InE with cefazolin could be dependent upon distributions of MSSA genotypes. Cefazolin can likely be used for the treatment of MSSA bacteraemia (except endocarditis), without consideration of an InE.