Objectives: Evaluation of the efficacy of empirical aminoglycoside in critically ill patients with bloodstream infections caused by extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E BSI). Methods: Patients treated between 2011 and 2018 for ESBL-E BSI in the ICU of six French hospitals were included in a retrospective observational cohort study. The primary endpoint was mortality on day 30. Results: Among 307 patients, 169 (55%) were treated with empirical aminoglycoside. Death rate was 40% (43% with vs. 39% without aminoglycoside, p = 0.55). Factors independently associated with death were age ≥70 years (OR: 2.67; 95% CI: 1.09–6.54, p = 0.03), history of transplantation (OR 5.2; 95% CI: 1.4–19.35, p = 0.01), hospital acquired infection (OR 8.67; 95% CI: 1.74–43.08, p = 0.008), vasoactive drugs >48 h after BSI onset (OR 3.61; 95% CI: 1.62–8.02, p = 0.001), occurrence of acute respiratory distress syndrome (OR 2.42; 95% CI: 1.14–5.16, p = 0.02), or acute renal failure (OR 2.49; 95% CI: 1.14–5.47, p = 0.02). Antibiotherapy appropriateness was more frequent in the aminoglycoside group (91.7% vs. 77%, p = 0.001). Rate of renal impairment was similar in both groups (21% vs. 24%, p = 0.59). Conclusions: In intensive care unit (ICU) patients with ESBL-E BSI, empirical treatment with aminoglycoside was frequent. It demonstrated no impact on mortality, despite increasing treatment appropriateness.