INTRODUCTION: This study aimed to assess the effectiveness of the emergency department observation unit (EDOU) for patients with acute pyelonephritis in a Singapore tertiary academic medical centre. METHODS: We reviewed the clinical records of consecutive patients who presented with pyelonephritis between 1 July 2012 and 31 October 2014 to collect information on demographics, symptoms, signs, laboratory and radiological results, treatment, and clinical outcomes. RESULTS: Of 459 emergency department (ED) patients who were identified as having pyelonephritis, 164 (35.7%) were managed in the EDOU. Successful management in the EDOU was achieved in 100 (61.0%) patients. Escherichia coli was the predominant (64.6%) micro-organism in urine cultures and was positive in 106 patients. Patients diagnosed with acute pyelonephritis who were successfully managed in the EDOU had a lower incidence of nausea (32.0% vs. 60.9%, p < 0.001) and vomiting (15.0% vs. 50.0%, p < 0.001) compared to those who were not successful. CONCLUSION EDOU is useful for both observation and treatment of patients with acute pyelonephritis. Urine cultures are sufficient for the identification of the culprit micro-organism. Patients who present with prominent symptoms of vomiting should have routine administration of antiemetics, while consideration for second-line antiemetics is recommended for those with persistent symptoms.