Background: Medicines in livestock production are certain as they are essential for the treatment or prevention of diseases, and the improvement of growth and productivity. Medicine use is rational when patients receive the appropriate medicines, the right doses, for an adequate period, and at the lowest cost. When one or more of these conditions is not met we call it irrational use which causes ineffective treatment, unnecessary waste of resources, and harm to patients; also residues cause public health issues (resistance, allergy, toxicity, and disturb normal gut microbiome) when used in food animals. Aim: To evaluate veterinary drug use patterns in livestock and to show the public health significance of irrational drug use. Methods: A cross-sectional and retrospective study was conducted from November 2019 to June 2020 at the Gondar town veterinary clinic. A total of 2117 drugs were prescribed to 1717 veterinary patients randomly selected from the case registry in this study. Results: The average number of drugs prescribed per case was 1.23 and the maximum number of drugs prescribed was 3. The percentages of antimicrobial, anthelmintic, endectocide and other drugs prescribed were 1182 (55.7%), 481 (22.7%), 426 (20.1%), and 28 (1.3%), respectively. All patients were treated without correct laboratory support. As a result, antimicrobials were inappropriately prescribed in 1.4% of viral diseases, 0.2% of external parasitic diseases, 0.8% of internal parasitic diseases, 0.3% of metabolic diseases, 0.1% of fungal diseases, and anthelmintic in 0.1% of bacterial diseases and 0.5% of external parasitic diseases. 2013/2117 (95.1%) the route of administration of the prescribed drugs was not stated. Clinic professionals were 80% animal health assistants and 20% veterinarians. Conclusion: The results reveal problems with correct diagnosis, low level of education of prescribers, few essential drugs, absence of standard veterinary drug lists, and inappropriate drug use. Therefore, laboratory facilities, educational level, key essential drugs, and standard drug list should fulfilled and improved accordingly and available drugs be prescribed in appropriate doses, routes, and regimens.