Background: For early recognition of patients with sepsis, quick Sequential Organ Failure Assessment (qSOFA) was proposed by Sepsis-3 criteria as initial sepsis identification outside of intensive care units. However, the new definition has subsequently led to controversy and prompted much discussion for delayed treatment efforts. We aimed to validate Sepsis-3 criteria on bacteremia patients by investigating prognostic impacts of inappropriate administration of empirical antimicrobial therapy (EAT) and delayed source control (SC) compared to Sepsis-2 criteria.Methods: In the multicenter cohort of adults with community-onset bacteremia in emergency departments (EDs), adverse effects of delayed treatment efforts on 30-day mortality were examined in septic and non-septic patients by fulfilling the Sepsis-2 or Sepsis-3 criteria using the Cox regression model after adjusting independent determinants of mortality.Results: Of the 3,898 total adults, septic patients accounted for 92.8% (3,619 patients) by Sepsis-2 criteria (i.e., SIRS criteria). Using Sepsis-3 criteria, 1,827 (46.9%) patients were diagnosed with early sepsis (i.e., initial qSOFA scores ≥ 2) in EDs and 2,622 (67.3%) with sepsis during hospitalization (i.e., increased SOFA scores of ≥ 2 from ED arrival). The prognostic impacts of inappropriate EAT or delayed SC (for complicated bacteremia) were both significant in septic patients with fulfilling the Sepsis-2 or Sepsis-3 (i.e., SOFA) criteria, respectively. Meanwhile, these delayed treatment efforts trivially impact prognoses of non-septic patients recognized by the Sepsis-2 or Sepsis-3 (i.e., SOFA) definitions. Notably, prognostic effects of inappropriate EAT or delayed SC were disclosed for septic patients in EDs, specifically those with qSOFA scores of ≥ 2, and prognostic impacts of delayed treatment efforts remained significant for patients initially recognized early as being non-septic (i.e., initial qSOFA scores of