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To identify clinical and organizational factors associated with delays in antimicrobial therapy for septic shock.In a retrospective cohort of critically ill patients with septic shock.Twenty-four ICUs.A total of 6,720 patients with septic shock.None.Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p < 0.0001); older age (+16 min per 10 yr; p < 0.0001); presence of comorbidities (+35 min; p < 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p < 0.0001), between 3 and 7 days (+121 min; p < 0.0001), and longer than 7 days (+130 min; p < 0.0001); and a diagnosis of pneumonia (+45 min; p < 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (–53 min; p < 0.001) and higher temperature (–15 min per 1°C; p < 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p< 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p < 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, –47 min; p< 0.001) had shorter times to antimicrobial therapy.We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.