Background: Appropriate prescription of antibiotics, consistent with nationally approved guidelines for the management of patients with respiratory tract infections (RTI) is an important step to reduce antibiotics resistance. This study assessed the appropriateness and factors associated with antibiotic prescription among RTI outpatients at the Tema Polyclinic in Ghana.Methods: Records of 600 outpatients diagnosed with at least one RTI condition between 1st July and 31st December, 2018 were manually retrieved and assessed in an analytic cross-sectional study. The outcomes were the proportion of RTI cases appropriately managed with antibiotics using Kunin’s modified criteria and antibiotic prescription. Independent variables included sociodemographic factors, clinical factors and prescriber’s professional category. Univariable logistic regression was used to estimate crude odds ratios for factors associated with antibiotic prescription. A threshold of p< 0.20 was used to include factors into a multivariable logistic regression model. Adjusted odds ratios were estimated using backward stepwise logistic regression. Statistical significance was set at p< 0.05. Results: The proportion of RTI cases which were prescribed with at least one antibiotic was 59.7% (358/600). Majority of RTI cases (68.2%) had non-specific diagnoses. Of the 32.8% (121/600) with specific diagnoses, (63.3%, 95% CI: 56.2, 69.9) were appropriately prescribed with antibiotics. Inadequate dosage duration accounted for most of the inappropriately prescribed antibiotics. The factors which were independently associated with reduced odds of antibiotic prescription were presenting with catarrh, diagnosis of rhinitis, acute respiratory tract infection, upper respiratory tract infection, and common cold. Requesting laboratory investigations, presenting with breathlessness, headache and sputum production were associated with increased odds of antibiotic prescription in the adjusted model.Conclusion: Majority of patients with specific diagnoses were prescribed antibiotics appropriately. However, most cases could not be evaluated for appropriateness because the diagnoses were non-specific. The frequency of antibiotic prescription was high. Antibiotic stewardship efforts should focus on imparting knowledge on specific diagnoses and corresponding treatment with emphasis on dosage regimen while deemphasizing symptomatic treatment based on sputum production. more...