Background: Misguided prescription of antibiotics is an important contributor towards the emergence and spread of antibiotic resistance. The absence of effective interventions to control antibiotic use leads to increased consumption beyond the needed requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the controlled use of antibiotics. The objective of this study was to determine the factors associated with antibiotic prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana.Methods: Secondary data obtained from the medical records of 2,519 febrile outpatients, consecutively sampled at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2016 was used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotic prescription. Results: The prevalence of antibiotic prescription was 70.1% (95% CI: 67.7-72.4). Prescribers with more years of practice (>5years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p < 0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) folds odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to receive antibiotics compared with those under 5 years (AOR=0.40, 95% CI: 0.32, 0.51; p<0.001). Patients referred for laboratory investigations were 29% less likely to be prescribed for antibiotics than those not referred. The presence of cough as a presenting symptom was associated with a 3.5 (95% CI: 2.54, 4.92) fold odds of antibiotic prescription. Conclusion: Prescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotics prescribing. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibiotics.