Appropriate antibiotic prescribing is important for good patient care and reducing the development of resistance. There has been limited research into doctors' prescribing practices. The aim of this study is to evaluate antibiotic prescribing practices in an Australian emergency department compared with the Therapeutic Guidelines. A case vignette survey was sent to emergency department doctors at The Townsville Hospital between February and May 2016. Antibiotic choices were assessed for appropriateness using the National Antimicrobial Prescribing Survey guidelines. Factors associated with antibiotic choice were assessed according to case, clinician experience and rationale. Data was analysed using a non-parametric Kruskal-Wallis test. Post-hoc analysis of variance was performed using Dunn test with Bonferroni correction for multiple simultaneous comparisons, with p<0.05 considered significant. 197 of 274 antibiotic choices (72%) were appropriate with 149 (54%) optimal. Antibiotic choice was more likely to be appropriate for a urinary tract infection (UTI) compared with severe pyelonephritis (p<0.01), severe cellulitis (p<0.01), moderate community-acquired pneumonia (CAP) (p<0.01) and sepsis (p<0.01), and was more likely to be appropriate for cellulitis than CAP (p=0.03) and sepsis (p=0.02). Antibiotic choices were more likely to be appropriate when doctors reported basing antibiotic choice on the Therapeutic Guidelines compared with current hospital practice (p=0.02). No significant difference was found in antibiotic appropriateness in relation to grade of doctor (p=0.34). This study demonstrates generally poor antibiotic prescribing compliance withthe Therapeutic Guidelines across all grades of clinician. Antibiotic prescribing was more likely to be appropriate if based on the Therapeutic Guidelines and in less severe infection.