Background Appropriate antimicrobial prescribing in the emergency department (ED) is a challenge due to diagnostic uncertainty, time pressure, and clinical inertia. Objective To assess the appropriateness of antimicrobial prescribing in the ED. Setting This study was conducted in the inpatient ED of a tertiary hospital in Malaysia. Method We conducted a 6-month retrospective antimicrobial prescriptions analysis among ED patients who received intravenous antimicrobial. Antimicrobial prescriptions of conveniently selected adult patients were evaluated with the medication appropriateness index. Main outcome measure Appropriateness of antimicrobial prescribing was the primary outcome measure. Results We analysed 310 patients with 326 antimicrobial prescriptions. Ceftriaxone (41.1%, n = 134) and amoxicillin-clavulanate (36.5%, n = 119) were the most common antimicrobials prescribed. Respiratory infections (71.5%, n = 233) was the main indication for antimicrobial therapy in the ED. All antimicrobials prescribed were indicated as per the Malaysian antimicrobial guidelines. The overall rate of inappropriate antimicrobial prescribing was 53.1% (n = 173). Thirty-two (9.8%) antimicrobials were prescribed with inappropriate doses; the majority was related to beta-lactam/beta-lactamase dose (p = 0.002). One hundred and forty-three (43.9%) antimicrobials prescribed had alternatives with similar efficacy but were less costly; which referring to ceftriaxone usage (p