BACKGROUND : Staphylococcus aureus (S. aureus) and streptococci are leading Gram-positive pathogens causing community-onset bacteremia. The comparisons of initial presentations and impacts of inappropriate empirical antimicrobial therapy (EAT) on clinical outcomes between the two pathogens are lacking. METHODS : In a 6-year cohort study, adult patients with community-onset monomicrobial S. aureus or streptococci bacteremia in the emergency department (ED) were studied. Clinical variables were collected retrospectively from medical records; the primary outcome was 4-week mortality after ED arrival. The Cox regression model was studied for effects of inappropriate EAT on 4-week mortality, after adjustment of independent predictors of 4-week mortality recognized by the multivariate regression model. RESULTS : A difference of clinical manifestations between S. aureus (291 patients) and streptococci (223) bacteremia was exhibited, in terms of bacteremia sources and comorbidity types, but bacteremia and comorbidity severity at ED arrival were similar. Furthermore, a longer period of the time-to-defervescence and hospitalization as well as more frequencies of septic metastasis were disclosed in S. aureus bacteremia, compared to streptococcal bacteremia. Of note, a significant impact (adjusted odds ratio [ORa], 2.23; 95% confidence interval [CI], 1.25-3.96) of inappropriate EAT on 4-week mortality was evidenced in S. aureus bacteremia, but not in streptococcal bacteremia (ORa, 2.88; 95% CI, 0.85-9.86). CONCLUSIONS : For adults having community-onset monomicrobial bacteremia, the similarity of bacteremia and comorbidity severity at ED arrivals were observed between causative microorganisms of S. aureus and streptococci, but a crucial impact of inappropriate EAT on short-term mortality was only observed in S. aureus.