Of the 139 patients with SA HVO, MRSA caused 62 (44.6%) cases. Patients infected with MRSA were more frequently of hospital-onset (35.5 vs. 13.0, P = .002) than MSSA-infected patients. Based on clinical and microbiological evaluation, a potential portal of entry for SA HVO was identified in 61 patients (43.9%). Intravenous venous catheters were more likely to be the origin in MRSA than in MSSA cases (46.7% vs. 22.6%, P = .048). The mortality rates for MRSA and MSSA HVO were similar (21.0% vs. 19.5%; P = .83). Longer duration of bacteremia (mean 10.1 vs. 3.1 days; P < .001), longer hospital stay (median 69 vs. 52 days; P = .001), and more frequent relapse (16.1% vs. 4.3%; P = .03) were observed among MRSA cases. Among the MRSA cases, relapse rates were lower in patients with a longer duration of antibiotic therapy: 41.7% (4–6 weeks), 25.0% (6–8 weeks), and 5.6% (≥8 weeks) (P = .007). Bacteremia was more likely to persist for ≥7 days in patients with an initial vancomycin trough <15 mg/L than in those with an initial trough ≥15 mg/L (79.3% vs. 20.0%; P = .001). A community-associated MRSA strain, specifically ST72-MRSA-SCCmec IV, was responsible for 70.8% of community-onset infections and 12.5% of hospital-onset infections.