Carbapenem-resistant Gram-negative bacterial bloodstream infection (CRGNB-BSI) has become a rapidly growing global threat with limited antibiotic options and significant mortality. The aim of this study was to explore the antibiotic strategies and clinical outcomes of patients with CRGNB-BSI in Western China. We retrospectively investigated the demographic, microbiological and clinical characteristics of 355 patients with CRGNB-BSI from 2012–2017. Treatment failure and 28-day in-hospital mortality rates were 49.3% (175/355) and 23.7% (84/355), respectively. The most frequently isolated micro-organism was Acinetobacter baumannii (58.6%; 208/355). Patients with treatment failure had higher procalcitonin and interleukin-6 levels (P < 0.05). High-dosage tigecycline therapy (200 mg loading dose followed by 100 mg every 12 h) was not superior to standard tigecycline dosing (P > 0.05). Multivariable analysis revealed that multiple organ dysfunction syndrome (MODS) (OR = 2.226, 95% CI 1.376–3.602; P = 0.001) and intensive care unit (ICU) admission (OR = 3.116, 95% CI 1.905–5.097; P = 0.000) were independent risk factors for treatment failure, whereas monotherapy (OR = 0.386, 95% CI 0.203–0.735; P = 0.004) had a protective effect. Survival analysis revealed that inappropriate therapy, MODS and ICU admission were associated with a higher 28-day in-hospital mortality rate (P < 0.001). Combination antimicrobial therapy was not superior to monotherapy (P = 0.387). This study demonstrates that appropriate therapy is significantly associated with lower treatment failure and 28-day in-hospital mortality rates. Tigecycline might not be a suitable option for CRGBN-BSI. Patients with MODS and admitted to the ICU had poor clinical outcomes.