Background: Staphylococcus aureus is one of the leading pathogens isolated from bloodstream infections (BSIs), and vancomycin has been the main choice to treat MRSA (methicillin-resistant S. aureus) infections. Vancomycin-intermediate S. aureus (VISA) and heteroresistant-VISA (hVISA) have been described, limiting this antibiotic use. We evaluated aspects associated with the resistance and its clonality of the S. aureus isolated from BSIs, and we determined their association with clinical aspects of patients attended at Rio de Janeiro between 2016 and 2018. The detection of MRSA and trimethoprim-sulfamethoxazole resistant isolates was performed using the disk diffusion test, while the minimum inhibitory concentrations (MICs) were evaluated for 5 antimicrobials using the broth microdilution method. The MICs for ceftaroline and vancomycin of the MRSA isolates were determined using the E test. The presence of hVISA isolates was evaluated for isolates with vancomycin MICs of 1 and 2 μg/mL by screening on BHI agar added with vancomycin. The population profile was divided by the area under the curve (ie, PAP/AUC test). SCC mec was evaluated by PCR and the clonal profile by PFGE method. Among 123 S. aureus isolates from BSI, 31% were MRSA. MIC50 and MIC90 were daptomycin 2 and 2 μg/mL; linezolid, 1 and 1 μg/mL; oxacillin 1 and 256 μg mL; teicoplanin, 0.5 and 0.5 μg/mL and vancomycin 1 and 1 μg/ml. MIC values for ceftaroline and vancomycin were 0.75 and 2 μg/mL. The frequency of isolates not susceptible to daptomycin was 75%. The clonal lineages and SCCmec types found were USA100/ST5-II (50%), USA800/ST5-IV (22%), USA300/ST8-IV (15.8%), USA1100/ST30-IV (5.3%), BEC/ST239-III (5.3%), and 1 isolate carrying SCCmecV/ST1. We found 1 VISA isolate, and the PAP/AUC analysis detected 3 hVISA isolates that were associated with the USA100 and USA300 lineages. Overall, 85% of patients had a vascular catheter. More advanced age was associated with MRSA infection as was higher mortality. Patients with end-stage renal disease were more affected by MSSA infection. Daptomycin nonsusceptibility and VISA and hVISA phenotypes associated with prevalent clonal lineages were described. In addition, MRSA infections presented higher mortality, which emphasizes the importance of epidemiological studies.