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Objectives: To assess the appropriateness of empirical antimicrobial therapy for sepsis and septic shock and determine factors associated with patient treatment outcomes at a Vietnamese national hospital., Methods: A cross-sectional study was conducted on 134 patients diagnosed with sepsis and/or septic shock at Thong-Nhat Hospital, Ho Chi Minh City, Vietnam, from January 2018 to June 2018. Appropriateness of antimicrobial therapy was defined as physician adherence to antimicrobial guidelines using the Sanford Guide to Antimicrobial Therapy and the Vietnam national guidelines. Bayesian model averaging technique was used to identify the related factors associated with patient treatment outcomes., Results: The median age of patients was 70 years. Organisms were identified in 54.5% of cases and predominated by Escherichia coli and staphylococci. Appropriate empirical antimicrobial agents were initiated in 56.6% ( n  = 73) of all cases. Of these patients, 31 cases (42.5%) and 61 cases (83.6%) received the antimicrobials in accordance with recommendations related to dosage and route of administration, respectively, bringing the overall rate of appropriate empirical antimicrobial therapy down to 23.3%. Patients who progressed to septic shock, received inappropriate antimicrobial therapy and required ICU admission were more likely to suffer treatment failure., Conclusions: The study findings suggest that clinicians should appropriately adhere to antimicrobial guidelines, especially in patients with septic shock and those who require ICU care, to improve treatment outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)