Background: Antimicrobial drug therapy problems refer to incorrect and inappropriate utilization of antimicrobials which affect patient's health outcomes and results in bacterial resistance. Incorrect use of antimicrobial agents is a key driver for the spread of antimicrobial drug resistance. Improving drug therapy problems has an important effect on the patients' health, treatment costs, and enhancing patients' quality of life. Hence, the aim of the present study was to assess antimicrobial drug therapy problems among patients in the Outpatient Department of Ataye hospital, Northeast Ethiopia. Methods: A hospital-based retrospective cross-sectional study design was used to assess antimicrobial drug therapy problems among patients in Ataye hospital from September 2018 to February 2019. Data were collected by trained graduating pharmacy students by reviewing medical records of patients using checklists and questionnaires. Results: A total of 248 patient cards were included in this study. At least one antimicrobial drug therapy problem had occurred among 96 (38.7%) of the study participants. The most common drug therapy problem was the need for additional drug therapy which was incurred by 38 (15.3%) of the study participants and ineffective antimicrobial therapy was experienced by 22 (8.9%) of the patients. Tetracyclines 25 (26%), fluoroquinolones 19 (19.8%), and penicillins 18 (18.8%) were the most common classes of antimicrobials prone to drug therapy problems. Conclusion: The current study revealed that nearly two-fifths of the study participants had experienced at least one form of antimicrobial drug therapy problem. The most common drug therapy problem was the need for additional drug therapy and the use of ineffective antimicrobial therapy. Tetracyclines, fluoroquinolones, and penicillins were the main classes of antimicrobials involved in the drug therapy problem.